KMT2A

Summary

Gene Symbol: KMT2A
Description: lysine methyltransferase 2A
Alias: ALL-1, CXXC7, HRX, HTRX1, MLL, MLL1, MLL1A, TRX1, WDSTS, histone-lysine N-methyltransferase 2A, CXXC-type zinc finger protein 7, lysine (K)-specific methyltransferase 2A, lysine N-methyltransferase 2A, mixed lineage leukemia 1, myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila), trithorax-like protein, zinc finger protein HRX
Species: human

Top Publications

  1. ncbi Prognosis of endometrial carcinoma stage I in two Swedish regions. A study with special regard to the effects of intracavitary irradiation with high dose-rate afterloading technique or with low dose-rate radium
    B Sorbe
    Department of Gynecologic Oncology, Orebro Medical Center Hospital, Sweden
    Acta Oncol 29:29-37. 1990
  2. pmc Molecular characterization of HTLV-1 Tax interaction with the KIX domain of CBP/p300
    Julita A Ramírez
    Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523 1870, USA
    J Mol Biol 372:958-69. 2007
  3. pmc Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes
    Debabrata Biswas
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 108:15751-6. 2011
  4. pmc Wilms' tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study
    Peter Paschka
    Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 26:4595-602. 2008
  5. pmc Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting
    Eric Schafer
    Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
    Blood 115:4798-809. 2010
  6. pmc Human RNA polymerase II-association factor 1 (hPaf1/PD2) regulates histone methylation and chromatin remodeling in pancreatic cancer
    Parama Dey
    Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
    PLoS ONE 6:e26926. 2011
  7. ncbi Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23)
    K Sano
    Department of Pediatrics, Kobe University School of Medicine, Kobe, Japan
    Blood 95:1066-8. 2000
  8. pmc Hypoxia-induced mixed-lineage leukemia 1 regulates glioma stem cell tumorigenic potential
    J M Heddleston
    Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44106, USA
    Cell Death Differ 19:428-39. 2012
  9. pmc The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection
    Aarthi Narayanan
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4 131, 4 Center Drive, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 104:10835-40. 2007
  10. ncbi Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters
    Hsien Sung Huang
    Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts 01604, USA
    J Neurosci 27:11254-62. 2007

Research Grants

  1. EPIDEMIOLOGY OF INFANT LEUKEMIA
    Julie Ross; Fiscal Year: 2007
  2. MARKUS MUSCHEN; Fiscal Year: 2016
  3. Post-translational regulation of MLL in leukemogenesis
    ANDREW GEORGE MUNTEAN; Fiscal Year: 2012
  4. ANDREW GEORGE MUNTEAN; Fiscal Year: 2014
  5. Hoxa9, Meis1, and Pbx in Self-renewal and Leukemogenesis
    Mark P Kamps; Fiscal Year: 2012
  6. Integrated Analyses of Taspase 1 (MLL Cleaving Protease)
    James J D Hsieh; Fiscal Year: 2010
  7. Jay L Hess; Fiscal Year: 2015
  8. Nancy J Zeleznik-Le; Fiscal Year: 2015
  9. Epigenetic manipulation of Leukemia
    H Leighton Grimes; Fiscal Year: 2010
  10. Jolanta Grembecka; Fiscal Year: 2015

Detail Information

Publications250 found, 100 shown here

  1. ncbi Prognosis of endometrial carcinoma stage I in two Swedish regions. A study with special regard to the effects of intracavitary irradiation with high dose-rate afterloading technique or with low dose-rate radium
    B Sorbe
    Department of Gynecologic Oncology, Orebro Medical Center Hospital, Sweden
    Acta Oncol 29:29-37. 1990
    ....
  2. pmc Molecular characterization of HTLV-1 Tax interaction with the KIX domain of CBP/p300
    Julita A Ramírez
    Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523 1870, USA
    J Mol Biol 372:958-69. 2007
    ..bind two distinct surfaces on the KIX domain: Tax binds KIX at the previously characterized mixed-lineage leukemia (MLL) protein interaction surface while pCREB binds KIX at the pKID-KIX interface...
  3. pmc Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes
    Debabrata Biswas
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 108:15751-6. 2011
    A number of acute leukemias arise from fusion of the mixed lineage leukemia 1 protein (MLL) N terminus to a variety of fusion partners that have been reported to reside in one or more poorly defined complexes linked to transcription ..
  4. pmc Wilms' tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study
    Peter Paschka
    Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 26:4595-602. 2008
    ..for the presence of FLT3 internal tandem duplications (FLT3-ITD), FLT3 tyrosine kinase domain mutations (FLT3-TKD), MLL partial tandem duplications (MLL-PTD), NPM1 and CEBPA mutations, and for the expression levels of ERG and BAALC.
  5. pmc Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting
    Eric Schafer
    Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
    Blood 115:4798-809. 2010
    Cooperating leukemogenic events in MLL-rearranged (MLL-r) infant acute lymphoblastic leukemia (ALL) are largely unknown...
  6. pmc Human RNA polymerase II-association factor 1 (hPaf1/PD2) regulates histone methylation and chromatin remodeling in pancreatic cancer
    Parama Dey
    Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
    PLoS ONE 6:e26926. 2011
    ..Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues...
  7. ncbi Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23)
    K Sano
    Department of Pediatrics, Kobe University School of Medicine, Kobe, Japan
    Blood 95:1066-8. 2000
    The mixed lineage leukemia (MLL) gene located at chromosome band 11q23 is frequently rearranged in patients with therapy-related acute monocytic leukemia who received topoisomerase II inhibitors...
  8. pmc Hypoxia-induced mixed-lineage leukemia 1 regulates glioma stem cell tumorigenic potential
    J M Heddleston
    Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44106, USA
    Cell Death Differ 19:428-39. 2012
    ..Here we demonstrate that in GBM the histone methyltransferase mixed-lineage leukemia 1 (MLL1) is induced by hypoxia and enhances hypoxic responses...
  9. pmc The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection
    Aarthi Narayanan
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4 131, 4 Center Drive, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 104:10835-40. 2007
    ..In contrast, HCF-1 was required for recruitment of the histone methyltransferases Set1 and MLL1 (mixed-lineage leukemia 1), leading to histone H3K4 trimethylation and transcriptional activation...
  10. ncbi Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters
    Hsien Sung Huang
    Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts 01604, USA
    J Neurosci 27:11254-62. 2007
    ..Heterozygosity for a truncated, lacZ knock-in allele of mixed-lineage leukemia 1 (Mll1), a histone methyltransferase expressed in GABAergic and other cortical neurons, resulted in decreased H3K4 ..
  11. pmc SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation
    Vanessa Brès
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037 1099, USA
    Mol Cell 36:75-87. 2009
    ..We show here that SKIP also associates with c-Myc and Menin, a subunit of the MLL1 histone methyltransferase (H3K4me3) complex and that HIV-1 Tat transactivation requires c-Myc and Menin, but not ..
  12. doi Association of high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia
    Ronald W Stam
    Department of Pediatric Oncology Hematology, Erasmus Medical Center Sophia Children s Hospital, Rotterdam, The Netherlands
    Blood 115:1018-25. 2010
    b>MLL-rearranged acute lymphoblastic leukemia (ALL) represents an unfavorable type of leukemia that often is highly resistant to glucocorticoids such as prednisone and dexamethasone...
  13. pmc Protein-arginine methyltransferase 1 (PRMT1) methylates Ash2L, a shared component of mammalian histone H3K4 methyltransferase complexes
    Jill S Butler
    Department of Molecular Carcinogenesis at The Virginia Harris Cockrell Cancer Research Center, University of Texas M D Anderson Cancer Center Science Park, Smithville, Texas 78957, USA
    J Biol Chem 286:12234-44. 2011
    ..The oncoprotein Ash2L is a component of the mixed lineage leukemia (MLL) family members 1-4, Setd1A, and Setd1B mammalian histone H3K4 methyltransferase complexes and is essential to ..
  14. ncbi Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias
    I Nilson
    Department of Genetics, University of Erlangen Nurnberg, Germany
    Br J Haematol 93:966-72. 1996
    ..The results form the basis for a greater understanding of the translocations and other structural alterations of the gene that conserve the open reading frame and thus produce presumably oncogenic variants of the ALL-1 protein...
  15. ncbi Is t(10;11)(p11.2;q23) involving MLL and ABI-1 genes associated with congenital acute monocytic leukemia?
    Cristina Morerio
    Divisione di Ematologia ed Oncologia Pediatrica, Istituto Giannina Gaslini, Largo G Gaslini 5, 16148, Genova, Italy
    Cancer Genet Cytogenet 139:57-9. 2002
    ..Myelocytic types are common, and chromosome band 11q23 rearrangements at the MLL locus are characteristic genetic markers...
  16. ncbi t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (GUANOSINE 5' MONOPHOSPHATE SYNTHETASE) gene
    L D Pegram
    Division of Oncology, Joseph Stokes Jr Research Institute, The Children s Hospital of Philadelphia, Pennsylvania 19104 4318, USA
    Blood 96:4360-2. 2000
    The partner gene of MLL was identified in a patient with treatment-related acute myeloid leukemia in which the karyotype suggested t(3;11)(q25;q23). Prior therapy included the DNA topoisomerase II inhibitors, teniposide and doxorubicin...
  17. ncbi Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23)
    L Daheron
    Laboratoire d Hématologie CNRS FRE 2224, Poitiers University Hospital, CHU La Miletrie BP577, 86021 Poitiers Cedex, France
    Genes Chromosomes Cancer 31:382-9. 2001
    The mixed lineage leukemia, MLL, gene is frequently rearranged in patients with secondary leukemia following treatment with DNA topoisomerase II inhibitors...
  18. ncbi Identification of CBL, a proto-oncogene at 11q23.3, as a novel MLL fusion partner in a patient with de novo acute myeloid leukemia
    Jen Fen Fu
    Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan
    Genes Chromosomes Cancer 37:214-9. 2003
    We have shown that the CBL gene at 11q23.3, telomeric to MLL, was fused to MLL in an adult patient with de novo acute myeloid leukemia (FAB-M1)...
  19. pmc Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy
    Zhong Wang
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 455:1205-9. 2008
    ..in the maintenance of a specific subtype of poor prognosis human leukaemia, genetically defined by mutations of the MLL proto-oncogene...
  20. pmc MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein
    Zhen Biao Xia
    Department of Medicine, Molecular Oncology Program, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA
    Proc Natl Acad Sci U S A 100:8342-7. 2003
    The MLL (mixed-lineage leukemia) gene is involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia...
  21. ncbi WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development
    Joanna Wysocka
    Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA
    Cell 121:859-72. 2005
    ..Here we show that a common component of MLL1, MLL2, and hSet1 H3 K4 methyltransferase complexes, the WD40-repeat protein WDR5, directly associates with histone ..
  22. pmc The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes
    Jose Sierra
    Regulatory Biology Laboratory, The Salk Insitute for Biological Studies, La Jolla, California 92037, USA
    Genes Dev 20:586-600. 2006
    ..The beta-cat C-terminal activation domain associates with TRRAP/TIP60 and mixed-lineage-leukemia (MLL1/MLL2) SET1-type chromatin-modifying complexes in vitro, and we show that beta-cat promotes H3K4 trimethylation at ..
  23. pmc Histone and DNA methylation defects at Hox genes in mice expressing a SET domain-truncated form of Mll
    Rémi Terranova
    Centre d immunologie de Marseille Luminy, Institut National de la Santé et de la Recherche Médicale Centre National de la Recherche Scientifique, Case 906, 13288 Marseille Cedex 9, France
    Proc Natl Acad Sci U S A 103:6629-34. 2006
    The Mll gene is a member of the mammalian trithorax group, involved with the antagonistic Polycomb group in epigenetic regulation of homeotic genes. MLL contains a highly conserved SET domain also found in various chromatin proteins...
  24. pmc Proteolysis of MLL family proteins is essential for taspase1-orchestrated cell cycle progression
    Shugaku Takeda
    Molecular Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 20:2397-409. 2006
    Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper Hox gene expression in vitro. To investigate its functions in vivo, we generated Taspase1(-/-) mice...
  25. doi Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks
    Stacey M Southall
    Institute of Cancer Research, Chester Beatty Laboratories, Chelsea, London, UK
    Mol Cell 33:181-91. 2009
    The mixed-lineage leukemia protein MLL1 is a transcriptional regulator with an essential role in early development and hematopoiesis...
  26. doi Specific promoter methylation identifies different subgroups of MLL-rearranged infant acute lymphoblastic leukemia, influences clinical outcome, and provides therapeutic options
    Dominique J P M Stumpel
    Department of Pediatric Oncology Hematology, Erasmus Medical Center Sophia Children s Hospital, Rotterdam, The Netherlands
    Blood 114:5490-8. 2009
    b>MLL-rearranged infant acute lymphoblastic leukemia (ALL) remains the most aggressive type of childhood leukemia, displaying a unique gene expression profile...
  27. doi The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures
    A Benedikt
    Institute of Pharmaceutical Biology ZAFES, Goethe University of Frankfurt, Biocenter, Frankfurt Main, Germany
    Leukemia 25:135-44. 2011
    Expression of the AF4-MLL fusion protein in murine hematopoietic progenitor/stem cells results in the development of proB acute lymphoblastic leukemia...
  28. doi Fine-tuning the stimulation of MLL1 methyltransferase activity by a histone H3-based peptide mimetic
    Vanja Avdic
    University of Ottawa, Ottawa Institute of Systems Biology, 451 Smyth Rd, Roger Guindon Hall, Ottawa, ON K1H 8M5, Canada
    FASEB J 25:960-7. 2011
    ..moiety to the N terminus of histone H3 significantly enhances its binding to WDR5 and prevents the stimulation of MLL1 methyltransferase activity by the WDR5-RbBP5-Ash2L complex...
  29. pmc The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases
    Pamela Zhang
    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
    Nucleic Acids Res 40:4237-46. 2012
    In mammals, the SET1 family of lysine methyltransferases (KMTs), which includes MLL1-5, SET1A and SET1B, catalyzes the methylation of lysine-4 (Lys-4) on histone H3...
  30. doi FLT3 activation cooperates with MLL-AF4 fusion protein to abrogate the hematopoietic specification of human ESCs
    Clara Bueno
    Centre for Genomics and Oncological Research, Pfizer University of Granada Andalusian Regional Government, Granada, Spain
    Blood 121:3867-78, S1-3. 2013
    Mixed-lineage leukemia (MLL)-AF4 fusion arises prenatally in high-risk infant acute pro-B-lymphoblastic leukemia (pro-B-ALL)...
  31. pmc Automethylation activities within the mixed lineage leukemia-1 (MLL1) core complex reveal evidence supporting a "two-active site" model for multiple histone H3 lysine 4 methylation
    Anamika Patel
    From the Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, New York 13210
    J Biol Chem 289:868-84. 2014
    The mixed lineage leukemia-1 (MLL1) core complex predominantly catalyzes mono- and dimethylation of histone H3 at lysine 4 (H3K4) and is frequently altered in aggressive acute leukemias...
  32. ncbi A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias
    M Djabali
    Molecular Genetics Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037
    Nat Genet 2:113-8. 1992
    ..An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region...
  33. ncbi Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias
    D C Tkachuk
    Department of Pathology, Stanford University School of Medicine, California 94305
    Cell 71:691-700. 1992
    ..Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved ..
  34. ncbi The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene
    Y Gu
    Jefferson Cancer Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
    Cell 71:701-8. 1992
    ..This suggests that each 11q23 abnormality gives rise to a specific oncogenic fusion protein...
  35. pmc Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias
    S Ziemin-van der Poel
    Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637
    Proc Natl Acad Sci U S A 88:10735-9. 1991
    ..We have named this gene MLL (myeloid/lymphoid, or mixed-lineage, leukemia.
  36. ncbi Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations
    M J Thirman
    Department of Medicine, University of Chicago
    N Engl J Med 329:909-14. 1993
    ..Previously, we identified the chromosomal breakpoint region in leukemias with the common 11q23 translocations and subsequently cloned a gene named MLL that spans the 11q23 breakpoint.
  37. ncbi The HRX proto-oncogene product is widely expressed in human tissues and localizes to nuclear structures
    L H Butler
    University Department of Cellular Science, John Radcliffe Hospital, Oxford, UK
    Blood 89:3361-70. 1997
    Chromosomal rearrangement of the HRX (MLL, ALL-1, Htrx) gene situated at chromosome band 11q23 is one of the most frequent genetic changes in infant leukemias of myeloid and lymphoid lineage and in treatment-induced secondary leukemias...
  38. ncbi Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins
    T Rozovskaia
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 19:351-7. 2000
    ..SET-SET interactions might act in integrating the activity of ALL-1 (TRX and ASH1) protein molecules, simultaneously positioned at different maintenance elements and directing expression of the same or different target genes...
  39. pmc Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells
    K Fair
    Cancer Center, Medical Center, Loyola University Chicago, Maywood, Illinois 60153
    Mol Cell Biol 21:3589-97. 2001
    The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown...
  40. ncbi ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation
    Tatsuya Nakamura
    Kimmel Cancer Center and Department of Microbiology, Jefferson Medical College, Philadelphia, PA 19107, USA
    Mol Cell 10:1119-28. 2002
    ..In parallel, H3-K4 is methylated, and histones H3 and H4 are acetylated at this promoter...
  41. pmc Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization
    James J D Hsieh
    Howard Hughes Medical Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 23:186-94. 2003
    The mixed-lineage leukemia gene (MLL, ALL1, HRX) encodes a 3,969-amino-acid nuclear protein homologous to Drosophila trithorax and is required to maintain proper Hox gene expression...
  42. ncbi A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15
    Vandana Chinwalla
    Section of Hematology Oncology, Department of Medicine, University of Chicago, IL 60637, USA
    Oncogene 22:1400-10. 2003
    The mixed lineage leukemia gene (MLL, also known as HRX, ALL-1 and Htrx) located at 11q23 is involved in translocations with over 40 different chromosomal bands in a variety of leukemia subtypes...
  43. ncbi Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation
    Adolfo A Ferrando
    Department of Pediatric Oncology, Mayer 630, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Blood 102:262-8. 2003
    Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent in both infant and therapy-related leukemias...
  44. ncbi Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression
    James J D Hsieh
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 115:293-303. 2003
    The Mixed-Lineage Leukemia gene (MLL/HRX/ALL1) encodes a large nuclear protein homologous to Drosophila trithorax that is required for the maintenance of HOX gene expression...
  45. ncbi Expression of HOX genes in acute leukemia cell lines with and without MLL translocations
    Hilmar Quentmeier
    DSMZ German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany
    Leuk Lymphoma 45:567-74. 2004
    ..expression of the genes MEIS1, HOXA5, HOXA7 and HOXA9 has been reported to be correlated with the occurrence of MLL translocations...
  46. pmc Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression
    Akihiko Yokoyama
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Mol Cell Biol 24:5639-49. 2004
    b>MLL (for mixed-lineage leukemia) is a proto-oncogene that is mutated in a variety of human leukemias...
  47. pmc Binding to nonmethylated CpG DNA is essential for target recognition, transactivation, and myeloid transformation by an MLL oncoprotein
    Paul M Ayton
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Mol Cell Biol 24:10470-8. 2004
    The MLL gene is a frequent target for leukemia-associated chromosomal translocations that generate dominant-acting chimeric oncoproteins...
  48. pmc Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors
    Thomas A Milne
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:749-54. 2005
    ..We have recently shown that menin, the MEN1 protein product, interacts with mixed lineage leukemia (MLL) family proteins in a histone methyltransferase complex including Ash2, Rbbp5, and WDR5...
  49. pmc The MLL partial tandem duplication: evidence for recessive gain-of-function in acute myeloid leukemia identifies a novel patient subgroup for molecular-targeted therapy
    Susan P Whitman
    Department of Internal Medicine, Division of Hematology Oncology, The Ohio State University, Columbus, OH 43210, USA
    Blood 106:345-52. 2005
    b>MLL (ALL-1) chimeric fusions and MLL partial tandem duplications (PTD) may have mechanistically distinct contributions to leukemogenesis...
  50. pmc The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression
    Zhen Biao Xia
    Department of Medicine, Molecular Biology Program, and Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA
    Proc Natl Acad Sci U S A 102:14028-33. 2005
    b>MLL, involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia, has >50 known partner genes with which it is able to form in-frame fusions...
  51. pmc MLL associates specifically with a subset of transcriptionally active target genes
    Thomas A Milne
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:14765-70. 2005
    b>MLL (mixed-lineage leukemia) is a histone H3 Lys-4 specific methyltransferase that is a positive regulator of Hox expression...
  52. ncbi Regulation of MLL1 H3K4 methyltransferase activity by its core components
    Yali Dou
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA
    Nat Struct Mol Biol 13:713-9. 2006
    ..we report the first biochemical reconstitution of a functional four-component mixed-lineage leukemia protein-1 (MLL1) core complex...
  53. pmc Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase
    Mark D Allen
    Centre for Protein Engineering, Cambridge, UK
    EMBO J 25:4503-12. 2006
    ..The mixed-lineage leukaemia (MLL) CXXC domain selectively binds nonmethyl-CpG DNA, and is required for transformation by MLL fusion proteins that ..
  54. ncbi The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation
    Florian Diehl
    Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Germany
    Blood 109:1472-8. 2007
    ..Here, we investigated the role of the histone lysine methyltransferase MLL for angiogenic functions in human umbilical vein endothelial cells...
  55. ncbi Spliced MLL fusions: a novel mechanism to generate functional chimeric MLL-MLLT1 transcripts in t(11;19)(q23;p13.3) leukemia
    C Meyer
    Leukemia 21:588-90. 2007
  56. ncbi Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement
    M W J C Jansen
    Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
    Leukemia 21:633-41. 2007
    ..Ig) and T-cell receptor (TCR) gene rearrangement pattern, and the presence of mixed lineage leukemia (MLL) rearrangements...
  57. ncbi E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases
    Shweta Tyagi
    Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland
    Mol Cell 27:107-19. 2007
    ..During the G1-to-S phase transition, HCF-1 recruits the mixed-lineage leukemia (MLL) and Set-1 histone H3 lysine 4 methyltransferases to E2F-responsive promoters and induces histone methylation and ..
  58. ncbi Interaction of MLL amino terminal sequences with menin is required for transformation
    Corrado Caslini
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Cancer Res 67:7275-83. 2007
    Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias...
  59. pmc Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions
    Han Liu
    Molecular Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 21:2385-98. 2007
    Human chromosome 11q23 translocations disrupting MLL result in poor prognostic leukemias. It fuses the common MLL N-terminal approximately 1400 amino acids in-frame with >60 different partners without shared characteristics...
  60. ncbi MLL translocations, histone modifications and leukaemia stem-cell development
    Andrei V Krivtsov
    Division of Haematology Oncology, Children s Hospital, Department of Pediatric Oncology, and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 7:823-33. 2007
    Translocations that involve the mixed lineage leukaemia (MLL) gene identify a unique group of acute leukaemias, and often predict a poor prognosis...
  61. ncbi Human CpG binding protein interacts with MLL1, MLL2 and hSet1 and regulates Hox gene expression
    Khairul I Ansari
    Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019, USA
    Biochim Biophys Acta 1779:66-73. 2008
    Human encodes several histone H3-Lysine 4 (H3K4) specific methyl-transferases (HMTs) such as MLL1 (mixed lineage leukemia 1), MLL2, MLL3, hSet1 etc, that play critical roles in gene expression...
  62. pmc Loss of MLL PHD finger 3 is necessary for MLL-ENL-induced hematopoietic stem cell immortalization
    Jing Chen
    Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago Medical Center, University of Chicago, Chicago, Illinois, USA
    Cancer Res 68:6199-207. 2008
    Reciprocal chromosomal translocations at the MLL gene locus result in expression of novel fusion proteins, such as MLL-ENL, associated with leukemia...
  63. doi C/EBPalpha and C/EBPvarepsilon induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene
    H Matsushita
    Department of Laboratory Medicine, Tokai University School of Medicine, Kanagawa, Japan
    Oncogene 27:6749-60. 2008
    ..Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated...
  64. doi A conserved arginine-containing motif crucial for the assembly and enzymatic activity of the mixed lineage leukemia protein-1 core complex
    Anamika Patel
    Department of Biology, Syracuse University, Syracuse, New York 13244, USA
    J Biol Chem 283:32162-75. 2008
    The mixed lineage leukemia protein-1 (MLL1) belongs to the SET1 family of histone H3 lysine 4 methyltransferases...
  65. doi Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide
    Anamika Patel
    Department of Biology, Syracuse University, Syracuse, New York 13244, USA
    J Biol Chem 283:32158-61. 2008
    The mixed lineage leukemia protein-1 (MLL1) catalyzes histone H3 lysine 4 methylation and is regulated by interaction with WDR5 (WD-repeat protein-5), RbBP5 (retinoblastoma-binding protein-5), and the Ash2L (absent, small, homeotic discs-..
  66. pmc WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone H3-binding pocket
    Ji Joon Song
    Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 283:35258-64. 2008
    WDR5 is a component of the mixed lineage leukemia (MLL) complex, which methylates lysine 4 of histone H3, and was identified as a methylated Lys-4 histone H3-binding protein...
  67. pmc Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B
    Richard F Schlenk
    Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
    Haematologica 94:54-60. 2009
    ..The objectives of this study were to evaluate the prognostic impact of gene mutations and to identify predictive genetic factors for the all-trans retinoic acid treatment effect...
  68. doi Dynamic association of MLL1, H3K4 trimethylation with chromatin and Hox gene expression during the cell cycle
    Bibhu P Mishra
    Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington 76019, TX, USA
    FEBS J 276:1629-40. 2009
    ..Interestingly, MLL1, which is normally associated with transcriptionally active chromatins (G1 phase), dissociates from condensed ..
  69. doi New insights to the MLL recombinome of acute leukemias
    C Meyer
    Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology, ZAFES, University of Frankfurt, Frankfurt Main, Germany
    Leukemia 23:1490-9. 2009
    Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias...
  70. doi Overexpression of human histone methylase MLL1 upon exposure to a food contaminant mycotoxin, deoxynivalenol
    Khairul I Ansari
    Department of Chemistry and Biochemistry, The University of Texas at Arlington, TX 76019, USA
    FEBS J 276:3299-307. 2009
    ..inhibitors demonstrated that Src kinase families are involved in upstream events in DON-mediated upregulation of MLL1. Sequence analysis demonstrated that the MLL1 promoter contains multiple Sp1-binding sites and importantly, the ..
  71. pmc MLL associates with telomeres and regulates telomeric repeat-containing RNA transcription
    Corrado Caslini
    Department of Pathology, University of Michigan Medical School, 5214B Medical Science I, 1301 Catherine Avenue, Ann Arbor, MI 48109 0602, USA
    Mol Cell Biol 29:4519-26. 2009
    ..Here, we show that the histone 3/lysine 4 (H3/K4) HMT and the transcriptional regulator MLL associate with telomeres and contribute to their H3/K4 methylation and transcription in a telomere length-dependent ..
  72. pmc Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study
    Brian V Balgobind
    Department of Pediatric Oncology Hematology, Erasmus MC Sophia Children s Hospital, Rotterdam, The Netherlands
    Blood 114:2489-96. 2009
    ..In most cases, the MLL gene is involved, and more than 50 translocation partners have been described...
  73. pmc On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex
    Anamika Patel
    Department of Biology, Syracuse University, Syracuse, New York 13244, USA
    J Biol Chem 284:24242-56. 2009
    ..The mixed lineage leukemia protein-1 (MLL1) is a member of the SET1 family of H3K4 methyltransferases and is frequently rearranged in acute leukemias...
  74. pmc MLL fusions: pathways to leukemia
    Han Liu
    Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Biol Ther 8:1204-11. 2009
    Human leukemias with chromosomal band 11q23 aberrations that disrupt the MLL/HRX/ALL-1 gene portend poor prognosis...
  75. pmc E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases
    Shweta Tyagi
    Center for Integrative Genomics, University of Lausanne, Genopode, Lausanne, Switzerland
    EMBO J 28:3185-95. 2009
    ..through a short DHQY sequence with the cell-cycle regulator HCF-1 together with the mixed-lineage leukaemia (MLL) family of histone H3 lysine 4 (H3K4) methyltransferases...
  76. pmc A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit
    Gerd A Blobel
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Mol Cell 36:970-83. 2009
    Mixed lineage leukemia (MLL) and its metazoan Trithorax orthologs have been linked with the epigenetic maintenance of transcriptional activity...
  77. pmc Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL-dependent gene transcription
    Pei Yun Chang
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Mol Biol 400:137-44. 2010
    The MLL (mixed-lineage leukemia) proto-oncogene encodes a histone methyltransferase that creates the methylated histone H3K4 epigenetic marks, commonly associated with actively transcribed genes...
  78. pmc The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis
    Andrew G Muntean
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Cancer Cell 17:609-21. 2010
    b>MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein-mediated transcriptional activation are poorly understood...
  79. pmc Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint
    Han Liu
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nature 467:343-6. 2010
    ..Reconstitution of Mll(-/-) (Mll also known as Mll1) mouse embryonic fibroblasts with wild-type but not S516A or ΔSET mutant MLL rescues the S-phase checkpoint ..
  80. doi Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis
    Man Mohan
    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA
    Nat Rev Cancer 10:721-8. 2010
    ..RNA polymerase II (Pol II) elongation factor (ELL) was the first translocation partner of mixed lineage leukaemia (MLL) for which a biochemical function was determined...
  81. doi Histone methyltransferase MLL1 regulates MDR1 transcription and chemoresistance
    Hairong Huo
    Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, The University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08901, USA
    Cancer Res 70:8726-35. 2010
    ..We show that the mixed lineage leukemia 1 (MLL1) protein, a histone methyltransferase specific for H3K4, is required for MDR1 promoter methylation, ..
  82. pmc t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL
    Ashish R Kumar
    Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
    Leuk Res 35:305-9. 2011
    The most frequent MLL-gene rearrangement found in leukemia is a reciprocal translocation with AF4 on chromosome 4 resulting in the formation of the MLL-AF4 and the AF4-MLL fusion genes...
  83. pmc A novel non-SET domain multi-subunit methyltransferase required for sequential nucleosomal histone H3 methylation by the mixed lineage leukemia protein-1 (MLL1) core complex
    Anamika Patel
    Department of Biology, Syracuse University, Syracuse, New York 13244, USA
    J Biol Chem 286:3359-69. 2011
    ..activity requires a complex that includes WRAD (WDR5, RbBP5, Ash2L, and DPY-30), a complex that is part of the MLL1 (mixed lineage leukemia protein-1) core complex but that also exists independently of MLL1 in the cell...
  84. pmc An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain
    Fang Cao
    Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
    PLoS ONE 5:e14102. 2010
    ..We demonstrate that both Ash2L and the MLL1 SET domain are capable of binding to S-adenosyl-L- [methyl-(3)H] methionine in the MLL1 core complex...
  85. doi Structural and biochemical insights into MLL1 core complex assembly
    Vanja Avdic
    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
    Structure 19:101-8. 2011
    ..The crystal structure of WDR5 in ternary complex with RbBP5 and MLL1 reveals that both proteins binds peptide-binding clefts located on opposite sides of WDR5's β-propeller domain...
  86. doi Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia
    Rosa Montes
    Consejería de Salud Universidad de Granada, Granada, Spain
    Blood 117:4746-58. 2011
    Infant acute lymphoblastic leukemia harboring the fusion mixed-lineage leukemia (MLL)-AF4 is associated with a dismal prognosis and very brief latency...
  87. pmc The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation
    Lipeng Wu
    Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Cell 43:132-44. 2011
    ..e., H4 K16 acetylation and H2B K34 ubiquitylation) through MOF and MSL2 subunits. They also shed light on how an intricate network of chromatin-modifying enzymes functions coordinately in gene activation...
  88. pmc The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations
    Gang Huang
    Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Blood 118:6544-52. 2011
    The mixed-lineage leukemia (MLL) H3K4 methyltransferase protein, and the heterodimeric RUNX1/CBFβ transcription factor complex, are critical for definitive and adult hematopoiesis, and both are frequently targeted in human acute ..
  89. pmc Structural basis for WDR5 interaction (Win) motif recognition in human SET1 family histone methyltransferases
    Venkatasubramanian Dharmarajan
    Department of Biology, Syracuse University, Syracuse, New York 13244, USA
    J Biol Chem 287:27275-89. 2012
    Translocations and amplifications of the mixed lineage leukemia-1 (MLL1) gene are associated with aggressive myeloid and lymphocytic leukemias in humans...
  90. pmc De novo mutations in MLL cause Wiedemann-Steiner syndrome
    Wendy D Jones
    South West Thames Regional Genetics Service, St George s Hospital, University of London, London SW17 0RE, UK
    Am J Hum Genet 91:358-64. 2012
    ..Utilizing a whole-exome sequencing approach, we identified de novo mutations in MLL in five of the six individuals...
  91. pmc Histone methylase MLL1 has critical roles in tumor growth and angiogenesis and its knockdown suppresses tumor growth in vivo
    K I Ansari
    Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA
    Oncogene 32:3359-70. 2013
    ..Herein, we demonstrated that antisense-mediated knockdown of MLL1 induced cell-cycle arrest and apoptosis in cultured cells...
  92. doi In focus: MLL-rearranged leukemia
    J de Boer
    Molecular Haematology and Cancer Biology Unit, UCL Institute of Child Health, Great Ormond Street Hospital, London, UK
    Leukemia 27:1224-8. 2013
    ..mechanisms underlying oncogenesis in leukemias associated with rearrangement of the Mixed Lineage Leukemia (MLL) gene have received a considerable amount of attention over the last two decades...
  93. pmc Functional specificity of CpG DNA-binding CXXC domains in mixed lineage leukemia
    Laurie E Risner
    From the Molecular Biology Program, Loyola University Medical Center, Maywood, Illinois 60153
    J Biol Chem 288:29901-10. 2013
    The MLL CXXC domain binds nonmethylated CpG-containing DNA and is essential for the oncogenic properties of MLL fusion proteins...
  94. ncbi Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations
    G Cimino
    Jefferson Cancer Institute, Jefferson Cancer Center, Philadelphia, Pennsylvania
    Cancer Res 51:6712-4. 1991
    ..The breakpoints cluster in a small DNA region of less than 5.8 kilobases...
  95. ncbi Late-life depression in primary care. How well are we doing?
    D A Banazak
    Michigan State University, Department of Psychiatry, East Lansing 48824 1316, USA
    J Gen Intern Med 11:163-7. 1996
    ..To discover primary care physicians' attitudes toward their abilities to detect and treat depression in the elderly...
  96. ncbi Characterization of a t(10;11)(p13-14;q14-21) in the monoblastic cell line U937
    J Shipley
    Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Genes Chromosomes Cancer 13:138-42. 1995
    ..3-q22.1 and the MLL gene at 11q23...
  97. pmc Role of angiotensin AT1 and AT2 receptors in mediating the renal effects of angiotensin II in the anaesthetized dog
    K L Clark
    Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Limited, Ware, Hertfordshire
    Br J Pharmacol 109:148-56. 1993
    ..However, the inhibitory effect of PD123177 on renal vasoconstrictor responses to high doses of AII, raises the possibility that functionally important AT2 receptors are present in the canine renal vasculature...
  98. pmc Characterization of purinoceptors mediating depolarization of rat isolated vagus nerve
    D J Trezise
    Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge
    Br J Pharmacol 110:1055-60. 1993
    ..ADP), adenosine 5'-monophosphate (AMP), adenosine and adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-s; all 1 x 10-6 1 x 10-3M) evoked only small depolarizations of the vagus nerve, amounting to 47 +/- 2.5%, 40.8 +/- 7...
  99. ncbi Two new translocations involving the 11q23 region map outside the MLL locus in myeloid leukemias
    Emilia Giugliano
    Medicina Interna II, Dipartimento di Scienze Cliniche e Biologiche, Osp S Luigi Gonzaga, Orbassano, Italy
    Haematologica 87:1014-20. 2002
    ..leukemias, chromosomal translocations involving the 11q23 band are frequently, but not invariably, associated with MLL gene rearrangement and their finding is associated with a poor prognosis...
  100. ncbi Comorbidity as a correlate of length of stay for hospitalized patients with acute chest pain
    K Matsui
    Department Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
    J Gen Intern Med 11:262-8. 1996
    ..DESIGN: Prospective cohort study. SETTING: Urban teaching hospital. PATIENTS: All 1,261 patient aged 30 years or more who were admitted to this hospital after coming to the emergency department with ..
  101. ncbi [A nation-wide surveillance of pathogen in elderly patients with urinary tract infections. 2nd Report: Sensitivities of pathogen for oral antibacterial agents]
    J Kumazawa
    Department of Urology, Faculty of Medicine, Kyushu University
    Kansenshogaku Zasshi 69:797-810. 1995
    ..Antibacterial activities of 5 agents against all 1,511 strains were intensified in CPFX, OFLX, NFLX, CPDX and CCL in that order...

Research Grants77

  1. EPIDEMIOLOGY OF INFANT LEUKEMIA
    Julie Ross; Fiscal Year: 2007
    ..with acute myeloid leukemia (AML) and 75% of infants with acute lymphoblastic leukemia (ALL) present with an MLL gene rearrangement in their leukemia cells...
  2. MARKUS MUSCHEN; Fiscal Year: 2016
    ..In striking contrast, ALL cells with other cytogenetic abnormalities (e.g. BCR-ABL1- or MLL-AF4) lack expression of a functional pre-B cell receptor in virtually all cases...
  3. Post-translational regulation of MLL in leukemogenesis
    ANDREW GEORGE MUNTEAN; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): MLL associated leukemias account for up to 80% of infant myeloid leukemias and about 10% of adult leukemias demonstrating a need for a thorough understanding of the mechanisms that lead to ..
  4. ANDREW GEORGE MUNTEAN; Fiscal Year: 2014
    Project Summary/Abstract MLL associated leukemias account for up to 80% of infant myeloid leukemias and about 10% of adult leukemias demonstrating a need for a thorough understanding of the mechanisms that lead to transformation...
  5. Hoxa9, Meis1, and Pbx in Self-renewal and Leukemogenesis
    Mark P Kamps; Fiscal Year: 2012
    ..to cause acute myeloid leukemia (AML), and are downstream effectors of a group of human AML oncoproteins, including MLL fusions...
  6. Integrated Analyses of Taspase 1 (MLL Cleaving Protease)
    James J D Hsieh; Fiscal Year: 2010
    Chromosome 11q23 translocations disrupting human Mixed Lineage Leukemia (MLL)gene are found in 80% of infantile leukemia and almost all cases of treatment induced secondary acute myeloid leukemia (AML)...
  7. Jay L Hess; Fiscal Year: 2015
    ..with deregulation of these targets are strongly associated with rearrangement of the mixed lineage leukemia gene MLL, a histone H3 lysine 4 specific methyltransferase (involved in approximately 10% of all AML cases), mutation of ..
  8. Nancy J Zeleznik-Le; Fiscal Year: 2015
    ..provided by applicant): AF9 (MLLT3) was first identified as a fusion partner of the Mixed Lineage Leukemia (MLL) gene in acute myeloid leukemia...
  9. Epigenetic manipulation of Leukemia
    H Leighton Grimes; Fiscal Year: 2010
    ..HoxA9 is oncogenically activated by multiple chromosome 11 translocations involving MLL1 or Nup98 (e.g. MLLAf9, Nup98-HoxA9)...
  10. Jolanta Grembecka; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Chromosomal translocations that affect the proto-oncogene MLL (Mixed Lineage Leukemia) occur in aggressive human acute leukemias, both in children and adults...
  11. Martin W Hetzer; Fiscal Year: 2015
    ..Third, the interaction between Nup98 and mammalian MLL and Wdr5 may prove to be important in understanding Acute Myelogenous Leukemia (AML) and development-associated ..
  12. Kira Gritsman; Fiscal Year: 2014
    ..Specific Aim 3 will examine the roles of p110 and p110 in leukemic stem cell function in MLL-AF9-induced leukemia, which has been particularly difficult to target therapeutically...
  13. Inhibition of the MLL-AF4-AF9 Interaction in Pediatric Leukemia
    Andrew Napper; Fiscal Year: 2012
    ..provided by applicant): Childhood leukemia that develops following rearrangement of the mixed lineage leukemia (MLL) gene to give MLL fusion proteins is aggressive and very difficult to treat...
  14. Role of U19/Eaf2 in androgen-dependent prostate homeostasis
    Zhou Wang; Fiscal Year: 2013
    ..identified and termed ELL-associated factor (Eaf2), based on its association with ELL, a fusion partner of MLL in acute myeloid leukemia...
  15. Mechanism of action of TOP2-directed anticancer drugs
    Leroy F Liu; Fiscal Year: 2012
    ..Etoposide-induced t-AML is frequently associated with balanced translocations of the mixed lineage leukemia gene (MLL) and many MLL partner genes, resulting in the expression of MLL fusion proteins...
  16. Radiation Protectors and Radiation Therapy Coupled Chemoprevention
    David J Grdina; Fiscal Year: 2013
    ..To facilitate these studies, we will use the MLL-ELL knock-in mouse model that closely recapitulates the multistep process of transformation observed in human-..
  17. CHUNG JEN JAMES J CHOU; Fiscal Year: 2016
    ..kinase mutations in FLT-3, c-Kit, and Ras and constitutively active transcription factors such as STAT5 and chimera MLL relevant to disease outcome...
  18. Etiology of Alkylator-Induced Myeloid Leukemia
    Michelle M Le Beau; Fiscal Year: 2012
    ..g., MLL gene at 11q23. t-MDS/t-AML represents an important model for cancer for several reasons...
  19. Regulation of hematopoietic stem cell self-renewal by NUP98-HOXA9
    Christopher A Klug; Fiscal Year: 2013
    ..Loss of Mll, a mammalian trithorax homolog that functions to maintain Hox gene expression, results in the loss of adult LT-HSC ..
  20. Discovering small molecules that overcome differentiation arrest in acute myeloid
    David B Sykes; Fiscal Year: 2012
    ..Furthermore, the subset of leukemias which express a fusion oncoprotein involving the MLL (mixed lineage leukemia) gene are dependent upon the expression of HoxA9...
  21. Etiology of translocations in hematopoietic cells
    Christine A Richardson; Fiscal Year: 2012
    ..therapy-related acute myeloid leukemia (t-AML) and chromosomal translocations involving the mixed lineage leukemia (MLL) gene on chromosome band 11q23...
  22. Omar Abdel-Wahab; Fiscal Year: 2015
    ..In unbiased analyses we observed significant and reproducible increases in HOXA9, HOXA5, and MLL expression with ASXL1 loss following KD of ASXL1...
  23. Tobias Neff; Fiscal Year: 2015
    ..We propose to study the role of Ezh2 in a genetically defined model of acute leukemia mediated by MLL-AF9 that is well characterized in our laboratory...
  24. Functional Characterization of MLL Gene Fusions
    Michael A Caligiuri; Fiscal Year: 2013
    This application is for renewal of our NCI-funded R01 grant entitled: "Functional Characterization of MLL Gene Fusions" (last score:17.2 percentile)...
  25. Experimental Therapeutics of Leukemia
    John C Byrd; Fiscal Year: 2013
    ..This project will study the impact of select prognostic gene (FLT3 ITD, MLL PTD, NPM1, WT-1, CEBPA, KIT) mutations, aberrant gene (BAALC, ERG, FLT3, MN1 and EVI1) expression, and mRNA/miRNA ..
  26. JAMES DOUGLAS GRIFFIN; Fiscal Year: 2016
    ..on understanding cooperation of these alleles with other leukemia associated alleles, such as PML-RARa, C/EBPa, MLL and AML1-ETO, and in developing accurate murine models of JAK2V617F MPD for testing inhibitors developed in Project ..
  27. Mechanisms and Prevention of Etoposide-Induced Leukemia
    Jack C Yalowich; Fiscal Year: 2011
    ..by applicant): Etoposide (VP-16)-related secondary myeloid leukemias (t-AML) are most frequently associated with MLL gene translocations at 11q23...
  28. Transcriptional regulation of chromatin modifying complexes by noncoding RNAs
    KEVIN CHUN KAI WANG; Fiscal Year: 2012
    ..HOTTIP also binds to WDR5, a component of the chromatin modifying complex Mixed- Lineage Leukemia-1 (MLL-1), suggesting it may demarcate domains of chromosomal remodeling via interactions with MLL-1...
  29. Shaomeng Wang; Fiscal Year: 2016
    ..Specifically, recent studies have shown that histone H3 K4 methyltransferase MLL and its enzymatic activity are essential for both leukemic transformation and for survival of leukemic stem cells...
  30. Mechanisms of Leukemogenic Transformation by MLL-CALM
    Daniel Wechsler; Fiscal Year: 2009
    Chromosomal rearrangements involving the Mixed Lineage Leukemia (MLL) gene at chromosome 11q23 are frequently seen in leukemias...
  31. Chemical modulators of Tet-family proteins
    Anjana Rao; Fiscal Year: 2010
    ..ii) TET1 is an MLL partner in acute myeloid and lymphoid leukemia (AML, ALL), and TET2 is implicated in myelodysplastic syndromes and ..
  32. Cancer epigenetics: Understanding histone methylation in leukemia stem cells
    Gang Greg Wang; Fiscal Year: 2011
    ..H3K4Me3 is a prominent histone mark associated with euchromatin structure and active transcription. MLL, an H3K4me3-specific methyltransferase enzyme, is a famed leukemia oncogene, and gain-of-function mutation of MLL ..
  33. Robert G Roeder; Fiscal Year: 2015
    ..necessitate opposing coactivator functions, histone modifying factors such as the activating p300 acetyl- and SET1/MLL methyl-transferases, and other DNA-binding regulatory factors (C/EBPs) that act synergistically with PPAR?...
  34. Carolyn A Felix; Fiscal Year: 2014
    ..provided by applicant): Infant leukemias and chemotherapy related leukemias characterized by translocations of the MLL gene at chromosome band 11q23 are devastating, often fatal diseases with unique clinical and biological features...
  35. Endocrine Disruptors: Assessment of endocrine disruption activity, mechanism and
    Subhrangsu Mandal; Fiscal Year: 2010
    ..Importantly, we also found that mixed lineage leukemia (MLL) family of histone methyl-transferases that are crucial players in gene activation, interact with ERs and bind to ..
  36. Kathrin M Bernt; Fiscal Year: 2014
    ..development plan that seeks to understand the role of epigenetic changes in normal hematopoietic development and MLL-rearranged leukemia, while establishing an academic career in Hematopoietic Stem Cell Transplantation...
  37. Risk of Leukemia after Protracted Exposures to Low Doses of Ionizing Radiation
    LYDIA BOGDANIVNA ZABLOTSKA; Fiscal Year: 2013
    ..of leukemogenesis after radiation exposure would be obtained by conducting genetic tests of two oncogenes (AML1 and MLL) known to be associated both with ionizing radiation exposure and with increased risk of leukemia...
  38. Ali Shilatifard; Fiscal Year: 2015
    ..PUBLIC HEALTH RELEVANCE: The focus of this application is on a group of proteins (MLL1, Dot1, and AFF4), which are involved in the pathogenesis of childhood leukemia...
  39. Functions of Histone Ubiquitination and Methylation
    Zu Wen Sun; Fiscal Year: 2010
    ..Many human homologs of the H3 K4 methyltransferase SET1 (e.g., MLL, Mixed Lineage Leukemia) are also mutated or disrupted in a variety of human cancers...
  40. Siddhartha Mukherjee; Fiscal Year: 2016
    ..in long-term HSCs, and strikingly downregulated in cycling progenitors and in mouse and human AMLs caused by the MLL-AF9 translocation. Knockdown of Yes-1 in mouse HSCs caused entry into cell-cycle, and increase in proliferation...
  41. Yali Dou; Fiscal Year: 2016
    b>MLL1 (mixed lineage leukemia) protein plays important roles in normal and malignant hematopoiesis by regulating the expression of a specific group of genes...
  42. Critical functions specified by the MLL CXXC domain determine leukemogenic capaci
    NOAH WARREN BIRCH; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The Mixed Lineage Leukemia (MLL) gene is involved in chromosomal translocations which generate a fusion protein causing aggressive, acute leukemia with poor prognosis...
  43. KUMBLE SANDEEP PRABHU; Fiscal Year: 2016
    ..from C57BL/6 mice transplanted with hematopoietic stem cells (HSC) that express the fusion oncoproteins BCR-ABL or MLL-AF9 as models of chronic myelogenous leukemia (CML) and AML, respectively, and 2) M34+Sca1+kit+ LSCs from Balb/c ..
  44. Oxidative and nitrosative stress resistance of Cryptococcus neoformans
    Jennifer K Lodge; Fiscal Year: 2010
    ..In this aim we will localize Tsa1, Trx1, and Trx2 more specifically by co-localization studies with known proteins and determine the signals that are ..
  45. Gang Greg Wang; Fiscal Year: 2014
    ..H3K4Me3 is a prominent histone mark associated with euchromatin structure and active transcription. MLL, an H3K4me3-specific methyltransferase enzyme, is a famed leukemia oncogene, and gain-of-function mutation of MLL ..
  46. Min Gyu Lee; Fiscal Year: 2014
    ..Importantly, we previously showed that KDM6A interacts with the H3K4 methyltransferases mixed-lineage leukemia (MLL) 3/4 in a histone modifier complex...
  47. Roles of MLL histone methyalses in estrogen mediated regulation of HDLR-SRB1
    Subhrangsu Mandal; Fiscal Year: 2010
    ..In human, there are several MLL families of proteins such as MLL1, MLL2, MLL3, MLL4, etc...
  48. Molecular genetics of MLL-associated leukemia
    Manuel Diaz; Fiscal Year: 2009
    The focus of this program project is the study of MLL associated leukemogenesis...
  49. Treating type 2 diabetes with menin inhibitors
    Frank Leu; Fiscal Year: 2013
    ..in a histone methyltransferase protein complex (menin complex) and by disrupting menin from binding to its partner MLL (mixed lineage leukemia-1) in the complex, this leads to an increase in beta cell proliferation...
  50. Daniel A Lim; Fiscal Year: 2016
    ..This proposal focuses on Mll (Mixed lineage leukemia), a chromatin remodeling factor related to Drosophila Trithorax...
  51. Molecular Mechanisms of Impaired DAN Damage Response in Leukemia Pathogenesis
    James J D Hsieh; Fiscal Year: 2012
    ..Human chromosome band 11q23 translocation disrupting the MLL gene results in poor prognostic leukemias that carry pathognomonic MLL fusions...
  52. James J Hsieh; Fiscal Year: 2015
    ..Human chromosome band 11q23 translocation disrupting the MLL gene results in poor prognostic leukemias that carry pathognomonic MLL fusions...
  53. Ali Shilatifard; Fiscal Year: 2015
    ..Our studies during the past five years have considerably expanded our molecular understanding of the role of MLL1 and one of its translocation partners, the ELL protein...
  54. Colles Price; Fiscal Year: 2015
    ..b>MLL- associated leukemias represent a small amount (roughly 10%) of total acute leukemias and patients with MLL- ..
  55. The role and functional mechanism of a miRNA cluster, mir-17-92 in leukemogenesis
    Jianjun Chen; Fiscal Year: 2012
    ..observed that the miRNAs from this cluster are frequently overexpressed in various acute leukemias, particularly in MLL-rearrangement leukemia, although the degree of up-regulation varies between individual miRNAs...
  56. Identification of functional tumor-stromal interactions in the bone marrow
    BENJAMIN LEVINE EBERT; Fiscal Year: 2010
    ..We have shown that murine LSCs (generated by the misexpression of the human MLL-AF9 translocation gene) do not survive in vitro in isolation, but can proliferate and form self-renewing "..
  57. Targeted therapy for 11q23 acute leukemias
    Charles S Hemenway; Fiscal Year: 2012
    PROJECT SUMMARY Rearrangements of the MLL gene at chromosome 11q23 portend a poor prognosis in patients with acute leukemia...
  58. INGA HOFMANN ZHANG; Fiscal Year: 2014
    ..has no apparent effect on adult hematopoietic stem cell function and hematopoiesis, and leukemogensis mediated by MLL-AF9...
  59. Scott A Armstrong; Fiscal Year: 2016
    ..In specific aim 1 we will work to define a role for D0T1L inhibition in MLL- Rearranged ALL through characterization of a potent, specific D0T1L inhibitor that has remarkably selective anti-..
  60. Ashish Kumar; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Majority of infant leukemias involve rearrangements in the MLL gene and are most often fatal...
  61. Scott A Armstrong; Fiscal Year: 2014
    ..leukemias that bear chromosomal translocations at 11q23 possess rearrangements of the Mixed Lineage Leukemia gene (MLL, HRX, ALL-1)...
  62. MLL in maintenance and regulation of HOX gene expression
    Nancy J Zeleznik-Le; Fiscal Year: 2012
    b>MLL was first identified because it is involved in chromosomal translocations that result in leukemia. MLL is required for maintaining the proper expression of target genes, including some of the clustered HOX genes...
  63. THERAPEUTIC INDEX OF ACUTE LYMPHOBLASTIC LEUKEMIA
    Stephen E Sallan; Fiscal Year: 2010
    ..identify and screen small molecules capable of modulating relevant gene expression programs, such as the TEL/AML1, MLL and glucocorticoid resistance pathways...
  64. JOHN WINTER CALVERT; Fiscal Year: 2014
    ..Specific Aim 2 will investigate if H2S suppresses apoptosis and cardiac hypertrophy via Nrf2/Trx1- dependent signaling...
  65. STEVEN LYNN KUNKEL; Fiscal Year: 2016
    ..Th1 or a Th2 type pulmonary immune response, 2) To examine the mechanistic role of the histone methyl transferase, MLL, and the histone demethylase, JMJD3, on the development of a Th1 or Th2 dependent pulmonary inflammation using ..
  66. Peroxynitrite Decomposition Catalyst and Nitric Oxide Donor for Endotoxemia
    GARRY JOHN SOUTHAN; Fiscal Year: 2012
    ..BUN, creatinine, NGAL, AST, ALT, histology injury score, and serum concentrations of TNF-1, HMGB-1, IL-6, TRP14, Trx1, LC8, I:B1, IL-12, MIP-11, CXCL9, and CXCL10...
  67. The Role of MLL-AF9 in Acute Myeloid Leukemia
    James C Mulloy; Fiscal Year: 2010
    ..In this model, the MLL-AF9 (MA9) leukemia oncogene is used to transform primary human CD34+ cells and promotes a rapid acute myeloid ..
  68. MAPPING AND CLONING TRANSLOCATION BREAKPOINTS
    Janet Rowley; Fiscal Year: 2004
    ..The first group will be patients known to have rearrangements of MLL, TEL, or AML1 (Specific Aim 1)...
  69. BIOMARKERS OF TREATMENT RELATED LEUKEMIA
    CAROLYN FELIX; Fiscal Year: 2004
    ..are related to alkylating agent therapy and have chromosome 5 and/or 7 loss; about 40% have translocation of the MLL gene at chromosome band 11q23, which occurs in leukemias related to DNA topoisomerase II inhibitors...
  70. Molecular characterization of normal cytogenetics AML in older patients
    Guido Marcucci; Fiscal Year: 2009
    ..have been discovered, including internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations in the NPM1 and CEBPA genes high expression of the ERG and BAALC genes...
  71. 11Q23 LEUKEMIA--ANALYSIS OF SECONDARY LEUKEMIAS AND AF-4
    Peter Domer; Fiscal Year: 1999
    ..The 11q23 gene involved, first named MLL (Mixed Lineage Leukemia), is a putative zinc finger transcription factor...
  72. Screening for Inhibitors of MLL Translocation Proteins in Leukemia
    John Bushweller; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Chromosomal translocations that affect the proto-oncogene MLL (Mixed Lineage Leukemia) occur in aggressive human acute leukemia's, both in children and adults...
  73. Molecular Aspects of Myeloid Development and Leukemia
    Steven Ackerman; Fiscal Year: 2005
    ..The workshop focuses on genes located at translocation breakpoints in leukemia such as AML1, TEL, RARalpha, and MLL to name a few, as well as on genes that are aberrantly expressed due to epigenetic alterations or function ..
  74. MLL AF4 LEUKEMIA
    John Kersey; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): MLL-AF4 leukemia in humans has long been known to have a unique and distinctive biology with a lymphoid or mixed lineage phenotype, high incidence in infants and a poor prognosis...
  75. DEPENDENCE OF P53 ON THIOL MAINTENANCE PROTEINS
    Gary Merrill; Fiscal Year: 2001
    ..Unlike deletion of the TRR1 gene, deletion of both yeast thioredoxin genes (TRX1 and 2) does not affect p53 activity...
  76. Role of histone methyltransferases hDOTIL in leukemogenesis
    Yi Zhang; Fiscal Year: 2009
    ..Two proteins that we identified are AF10 and ENL, both of which are MLL (mix lineage leukemia) fusion partner involved in acute myeloid leukemia...
  77. Anticancer Agent Pharmacodynamics in Acute Leukemia
    Mary Relling; Fiscal Year: 2006
    ..clinical and biologic entity, characterized by a unique molecular signature: nonhomologous recombination of the MLL gene with one of a number of partner genes, resulting in leukemogenic genomic fusions...