D Gary Gilliland

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint The roles of FLT3 in hematopoiesis and leukemia
    D Gary Gilliland
    Brigham and Women s Hospital, Howard Hughes Medical Institute, Boston, MA, USA
    Blood 100:1532-42. 2002
  2. ncbi request reprint Focus on acute leukemias
    D Gary Gilliland
    Howard Hughes Medical Institute, Brigham and Women s Hospital, and Dana Farber Cancer Institute, Harvard Medical School, Harvard Institutes of Medicine, 4 Blackfan Circle, Room 418, Boston, Massachusetts 02115, USA
    Cancer Cell 1:417-20. 2002
  3. pmc MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia
    Yana Pikman
    Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e270. 2006
  4. pmc Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells
    Ann Mullally
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 17:584-96. 2010
  5. pmc JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model
    Thomas Mercher
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:2770-9. 2006
  6. pmc FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia
    Benjamin H Lee
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:367-80. 2007
  7. ncbi request reprint Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations
    M Golam Mohi
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, 77 Avenue Louis Pasteur, NRB 1030, Boston, Massachusetts 02115, USA
    Cancer Cell 7:179-91. 2005
  8. ncbi request reprint Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Cell 1:433-43. 2002
  9. pmc Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells
    Winnie F Tam
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Blood 112:1981-92. 2008
  10. ncbi request reprint Activating alleles of JAK3 in acute megakaryoblastic leukemia
    Denise K Walters
    Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Cancer Cell 10:65-75. 2006

Collaborators

Detail Information

Publications98

  1. ncbi request reprint The roles of FLT3 in hematopoiesis and leukemia
    D Gary Gilliland
    Brigham and Women s Hospital, Howard Hughes Medical Institute, Boston, MA, USA
    Blood 100:1532-42. 2002
    ..Taken together, these results suggest that FLT3 is an attractive therapeutic target for kinase inhibitors or other approaches for patients with mutations of this gene...
  2. ncbi request reprint Focus on acute leukemias
    D Gary Gilliland
    Howard Hughes Medical Institute, Brigham and Women s Hospital, and Dana Farber Cancer Institute, Harvard Medical School, Harvard Institutes of Medicine, 4 Blackfan Circle, Room 418, Boston, Massachusetts 02115, USA
    Cancer Cell 1:417-20. 2002
  3. pmc MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia
    Yana Pikman
    Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e270. 2006
    ....
  4. pmc Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells
    Ann Mullally
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 17:584-96. 2010
    ..These findings provide insights into the consequences of JAK2 activation on HSC differentiation and function and have the potential to inform therapeutic approaches to JAK2V617F-positive MPN...
  5. pmc JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model
    Thomas Mercher
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:2770-9. 2006
    ..These findings provide new insights into pathways and therapeutic targets that contribute to the pathogenesis of AMKL...
  6. pmc FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia
    Benjamin H Lee
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:367-80. 2007
    ..This model provides insights into the consequences of constitutive signaling by an oncogenic tyrosine kinase on hematopoietic progenitor quiescence, function, and cell fate...
  7. ncbi request reprint Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations
    M Golam Mohi
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, 77 Avenue Louis Pasteur, NRB 1030, Boston, Massachusetts 02115, USA
    Cancer Cell 7:179-91. 2005
    ..Shp2 mutants also cause myeloproliferation in Drosophila. Mek or Tor inhibitors potently inhibit transformation, suggesting new approaches to JMML therapy...
  8. ncbi request reprint Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Cell 1:433-43. 2002
    ..PKC412 is a potent inhibitor of mutant FLT3 and is a candidate for testing as an antileukemia agent in AML patients with mutant FLT3 receptors...
  9. pmc Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells
    Winnie F Tam
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Blood 112:1981-92. 2008
    ..These findings indicate that Id1 is an important target of constitutively activated tyrosine kinases and may be a therapeutic target for leukemias associated with oncogenic tyrosine kinases...
  10. ncbi request reprint Activating alleles of JAK3 in acute megakaryoblastic leukemia
    Denise K Walters
    Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Cancer Cell 10:65-75. 2006
    ..These findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis and demonstrate the utility of proteomic approaches to identifying clinically relevant mutations...
  11. ncbi request reprint MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors
    Brian J P Huntly
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Cell 6:587-96. 2004
    ..These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death...
  12. pmc Oncogenic K-ras cooperates with PML-RAR alpha to induce an acute promyelocytic leukemia-like disease
    Iris T Chan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:1708-15. 2006
    ....
  13. ncbi request reprint PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRα-induced myeloproliferative disease
    Jan Cools
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 3:459-69. 2003
    ..Our data establish PKC412 as molecularly targeted therapy for HES and other diseases expressing activated PDGFRalpha and demonstrate the potential of alternative kinase inhibitors to overcome resistance in target tyrosine kinases...
  14. ncbi request reprint Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles
    Stefan Fröhling
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 12:501-13. 2007
    ....
  15. doi request reprint Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera
    Gerlinde Wernig
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 13:311-20. 2008
    ....
  16. pmc Stable expression of small interfering RNA sensitizes TEL-PDGFbetaR to inhibition with imatinib or rapamycin
    Jing Chen
    Howard Hughes Medical Institute, Division of Hematology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 113:1784-91. 2004
    ..Although siRNA delivery in vivo is a challenging problem, stable expression of siRNA, which targets oncogenic fusion genes, may potentiate the effects of conventional therapy for hematologic malignancies...
  17. ncbi request reprint CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML)
    Louise M Kelly
    Division of Hematology Oncology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Cancer Cell 1:421-32. 2002
    ..Therapeutic efficacy of CT53518 was demonstrated both in a nude mouse model and in a murine bone marrow transplant model of FLT3-ITD-induced disease...
  18. ncbi request reprint FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress
    Zuzana Tothova
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 128:325-39. 2007
    ..Thus, FoxO proteins play essential roles in the response to physiologic oxidative stress and thereby mediate quiescence and enhanced survival in the HSC compartment, a function that is required for its long-term regenerative potential...
  19. pmc Constitutively active AKT depletes hematopoietic stem cells and induces leukemia in mice
    Michael G Kharas
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Blood 115:1406-15. 2010
    ..This study demonstrates that enhanced AKT activation is an important mechanism of transformation in AML and that HSCs are highly sensitive to excess AKT/mTOR signaling...
  20. pmc Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype
    Joseph D Growney
    Division of Hematology and Department of Pathology, Brigham and Women s Hospital, 1 Blackfan Circle, Boston, MA 02115, USA
    Blood 106:494-504. 2005
    ....
  21. pmc Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412
    Joseph D Growney
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Blood 106:721-4. 2005
    ..These findings suggest that PKC412 may be a useful therapeutic agent for c-KIT-positive malignancies harboring the imatinib mesylate-resistant D816V or D816Y activation mutations...
  22. pmc Ott1(Rbm15) has pleiotropic roles in hematopoietic development
    Glen D Raffel
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 104:6001-6. 2007
    ..It is plausible that dysregulation of Ott1-dependent hematopoietic developmental pathways, in particular those affecting the megakaryocyte lineage, may contribute to OTT1-MAL-mediated leukemogenesis...
  23. pmc Activation of FIP1L1-PDGFRalpha requires disruption of the juxtamembrane domain of PDGFRalpha and is FIP1L1-independent
    Elizabeth H Stover
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:8078-83. 2006
    ..These results suggest that disruption of the autoinhibitory JM domain is an alternative, dimerization-independent mechanism by which chimeric tyrosine kinases are constitutively activated and induce leukemogenesis...
  24. ncbi request reprint The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia
    Jan Cools
    Division of Hematology and the Howard Hughes Medical Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 103:2802-5. 2004
    ....
  25. pmc Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs
    M Golam Mohi
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, New Research Building, 330 Brookline Avenue, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:3130-5. 2004
    ..Similar strategies may be useful for treating solid tumors associated with mutant and/or overexpressed PTKs...
  26. pmc The small molecule tyrosine kinase inhibitor AMN107 inhibits TEL-PDGFRbeta and FIP1L1-PDGFRalpha in vitro and in vivo
    Elizabeth H Stover
    Division of Hematology, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    Blood 106:3206-13. 2005
    ..In summary, AMN107 can inhibit myeloid proliferation driven by TEL-PDGFRbeta and FIP1L1-PDGFRalpha and may be a useful drug for treatment of patients with myeloproliferative disease who harbor these kinase fusions...
  27. pmc Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model
    Gerlinde Wernig
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 107:4274-81. 2006
    ....
  28. pmc Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia
    Michael G Kharas
    Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Nat Med 16:903-8. 2010
    ....
  29. ncbi request reprint Prediction of resistance to small molecule FLT3 inhibitors: implications for molecularly targeted therapy of acute leukemia
    Jan Cools
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Cancer Res 64:6385-9. 2004
    ....
  30. ncbi request reprint Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 7:129-41. 2005
    ..AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL...
  31. pmc mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis
    Demetrios Kalaitzidis
    Division of Hematology Oncology, Children s Hospital Boston and Dana Farber Cancer Institute, Harvard Medical School and the Harvard Stem Cell Institute, Boston, MA 02115, USA
    Cell Stem Cell 11:429-39. 2012
    ..These data delineate critical roles for mTORC1 in hematopoietic function and leukemogenesis and inform clinical strategies based on chronic mTORC1 inhibition...
  32. pmc Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
    Melanie G Cornejo
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 118:1264-73. 2011
    ....
  33. pmc The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes
    Gerlinde Wernig
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Blood 111:3751-9. 2008
    ..Overall, our results suggest that constitutive activation of Jak2 requires an intact FERM domain for a transforming phenotype, and is necessary for activation of the major target of Jak2, STAT5...
  34. pmc Absence of the transcription factor CCAAT enhancer binding protein alpha results in loss of myeloid identity in bcr/abl-induced malignancy
    Katharina Wagner
    Harvard Institutes of Medicine, Room 954, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:6338-43. 2006
    ..Taken together, our study provides evidence that myeloid lineage identity of malignant hematopoietic progenitor cells requires the residual expression of C/EBPalpha...
  35. ncbi request reprint Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Cell 7:387-97. 2005
    ..In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase...
  36. ncbi request reprint Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518
    Jennifer J Clark
    Division of Hematology Oncology, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    Blood 104:2867-72. 2004
    ..These findings have implications for the evaluation of responses in clinical trials with FLT3 inhibitors and provide a strategy to screen for compounds that can overcome resistance...
  37. pmc PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder
    Jing Chen
    Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:14479-84. 2004
    ..Therefore, PKC412 may be a useful therapy for treatment of human stem cell leukemia-lymphoma syndrome...
  38. pmc The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model
    Thomas Mercher
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 119:852-64. 2009
    ....
  39. pmc Ott1 (Rbm15) is essential for placental vascular branching morphogenesis and embryonic development of the heart and spleen
    Glen D Raffel
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 29:333-41. 2009
    ..Thus, Ott1-dependent pathways, in addition to being implicated in leukemogenesis, may also be important for the pathogenesis of placental insufficiency and cardiac malformations...
  40. pmc Differential niche and Wnt requirements during acute myeloid leukemia progression
    Steven W Lane
    Division of Hematology Oncology, Children s Hospital Boston and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 118:2849-56. 2011
    ..These data identify differential engagement of HM associated with leukemic progression and identify an LSC niche that is physically distinct and independent of the constraints of Wnt signaling that apply to normal HSCs...
  41. pmc K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to gamma-secretase inhibitors
    Thomas Kindler
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Blood 112:3373-82. 2008
    ..These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways...
  42. ncbi request reprint Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML
    Jingrui Jiang
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, D720C, Boston, MA 02115, USA
    Blood 104:1855-8. 2004
    ..These results suggest that mutations at N841 represent a significant new activating mutation in patients with AML and that patients with such mutations may respond to small-molecule FLT3 inhibitors such as PKC412...
  43. pmc The Apc(min) mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS
    Steven W Lane
    Department of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 115:3489-97. 2010
    ....
  44. doi request reprint The JAK2(V617F) tyrosine kinase mutation in myeloproliferative disorders: Summary of published literature and a perspective
    Martha Wadleigh
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Curr Hematol Malig Rep 1:75-80. 2006
    ..This discovery has led to greater understanding of the molecular pathogenesis of the chronic myeloproliferative disorders, which may translate into targeted therapy...
  45. pmc The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis
    Claudia Scholl
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 117:1037-48. 2007
    ....
  46. pmc X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis
    Ross L Levine
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 107:4139-41. 2006
    ..In addition, some ET and MMM patients with clonal granulopoiesis have somatic mutations other than JAK2V617F...
  47. ncbi request reprint Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9
    Andrei V Krivtsov
    Division of Hematology Oncology, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 442:818-22. 2006
    ..Our findings define progression from normal progenitor to cancer stem cell, and suggest that targeting a self-renewal programme expressed in an abnormal context may be possible...
  48. pmc Cdx4 dysregulates Hox gene expression and generates acute myeloid leukemia alone and in cooperation with Meis1a in a murine model
    Dimple Bansal
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:16924-9. 2006
    ..Inasmuch as many human leukemias show dysregulated expression of a spectrum of HOX family members, these collective findings also suggest a central role for CDX4 expression in the genesis of acute leukemia...
  49. pmc Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD
    Jennifer L Rocnik
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:1339-45. 2006
    ....
  50. pmc Block of C/EBP alpha function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations
    Hanna S Radomska
    Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 203:371-81. 2006
    ....
  51. ncbi request reprint The retinoblastoma binding protein RBP2 is an H3K4 demethylase
    Robert J Klose
    Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell 128:889-900. 2007
    ..These studies provide mechanistic insights into transcriptional regulation by RBP2 and provide the first example of a mammalian enzyme capable of erasing trimethylated H3K4...
  52. pmc Constitutively activated FGFR3 mutants signal through PLCgamma-dependent and -independent pathways for hematopoietic transformation
    Jing Chen
    Howard Hughes Medical Institute, Harvard Medical Scgool, Boston, MA, USA
    Blood 106:328-37. 2005
    ..These data indicate that engagement of multiple signaling pathways, including PLCgamma-dependent and PLCgamma-independent pathways, is required for full hematopoietic transformation by constitutively activated FGFR3 mutants...
  53. doi request reprint Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells
    Claudia Scholl
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 137:821-34. 2009
    ....
  54. pmc Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models
    Melanie G Cornejo
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 113:2746-54. 2009
    ..These data demonstrate that constitutive JAK3 activation disrupts T-cell homeostasis and induces lymphoproliferative diseases in mice...
  55. ncbi request reprint Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation
    Jing Chen
    Division of Hematology, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    Blood 104:535-42. 2004
    ..Therefore, the WW-like domain in the context of TELPDGFbetaR may have both positive and negative regulatory roles in kinase activation...
  56. pmc The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia
    Ross L Levine
    Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 106:3377-9. 2005
    ..These data indicate that the JAK2V617F allele is present in acute and chronic myeloid malignancies but not in lymphoid malignancies...
  57. pmc AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias
    Stephen M Sykes
    Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell 146:697-708. 2011
    ..These data reveal a molecular role for AKT/FOXO and JNK/c-JUN in maintaining a differentiation blockade that can be targeted to inhibit leukemias with a range of genetic lesions...
  58. pmc Activating mutations in ALK provide a therapeutic target in neuroblastoma
    Rani E George
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 455:975-8. 2008
    ....
  59. doi request reprint Notch signaling specifies megakaryocyte development from hematopoietic stem cells
    Thomas Mercher
    Department of Medicine, Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 20115, USA
    Cell Stem Cell 3:314-26. 2008
    ..These findings indicate that Notch is a positive regulator of megakaryopoiesis and plays a more complex role in cell-fate decisions among myeloid progenitors than previously appreciated...
  60. pmc Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis
    Inga Hofmann
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Cell Stem Cell 4:559-67. 2009
    ..Furthermore, the Hh pathway may not be a compelling target in certain hematopoietic malignancies...
  61. ncbi request reprint The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera
    Ayalew Tefferi
    Division of Hematology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, and Department of Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Cancer 106:631-5. 2006
    ..Several studies have recently reported on the occurrence of a JAK2(V617F) mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study...
  62. doi request reprint STAT5 is crucial to maintain leukemic stem cells in acute myelogenous leukemias induced by MOZ-TIF2
    Winnie F Tam
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Cancer Res 73:373-84. 2013
    ..Therefore, targeting aberrantly activated STAT5 or rewired downstream signaling pathways may be a promising therapeutic option...
  63. ncbi request reprint KIAA1509 is a novel PDGFRB fusion partner in imatinib-responsive myeloproliferative disease associated with a t(5;14)(q33;q32)
    R L Levine
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Leukemia 19:27-30. 2005
    ..Imatinib therapy resulted in rapid normalization of the patient's blood counts, and subsequent bone marrow biopsies and karyotypic analysis were consistent with sustained complete remission...
  64. ncbi request reprint The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia
    Jan Cools
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Opin Hematol 11:51-7. 2004
    ....
  65. doi request reprint Deregulation of signaling pathways in acute myeloid leukemia
    Claudia Scholl
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Semin Oncol 35:336-45. 2008
    ..Eventually, it may become possible to use pathogenesis-oriented combinations of signal transduction inhibitors to improve the cure rate in AML patients...
  66. pmc A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9
    Ajeeta B Dash
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:7622-7. 2002
    ..Furthermore, these data indicate that despite acquisition of additional mutations, CML blast crisis cells retain their dependence on BCR/ABL for proliferation and survival...
  67. pmc Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease
    Iris T Chan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 113:528-38. 2004
    ..This model system will be useful for assessing the contribution of cooperating mutations in AML and testing ras inhibitors in vivo...
  68. pmc FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis
    Ji Hye Paik
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    Cell 128:309-23. 2007
    ..Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis...
  69. ncbi request reprint FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model
    Louise M Kelly
    Division of Hematology Oncology, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 99:310-8. 2002
    ..This model system should be useful to assess the contribution of additional cooperating mutations and to evaluate specific FLT3 inhibitors in vivo...
  70. pmc The leukemic stem cell niche: current concepts and therapeutic opportunities
    Steven W Lane
    Division of Hematology, Brigham and Women s Hospital, Boston, MA, USA
    Blood 114:1150-7. 2009
    ..Finally, we will discuss approaches for the rational development of therapies that target the microenvironment...
  71. ncbi request reprint Leukaemia stem cells and the evolution of cancer-stem-cell research
    Brian J P Huntly
    Brian J P Huntly is at the Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Nat Rev Cancer 5:311-21. 2005
    ....
  72. ncbi request reprint Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation
    Toshiyuki Araki
    Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, NRB1038, 330 Brookline Ave, Boston, Massachusetts 02215, USA
    Nat Med 10:849-57. 2004
    ....
  73. doi request reprint A radical bailout strategy for cancer stem cells
    Zuzana Tothova
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cell Stem Cell 4:196-7. 2009
    ..Their studies provide a link between the management of ROS by CSCs and enhanced tumor radioresistance...
  74. ncbi request reprint The role of signal transducer and activator of transcription factors in leukemogenesis
    David W Sternberg
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Clin Oncol 22:361-71. 2004
    ..This review discusses evidence for the functional importance of STAT activation in the biology of leukemia and current opportunities for modulating STAT proteins in the therapy of this group of diseases...
  75. ncbi request reprint FLT3-activating mutations in acute promyelocytic leukaemia: a rationale for risk-adapted therapy with FLT3 inhibitors
    D Gary Gilliland
    Howard Hughes Medical Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Best Pract Res Clin Haematol 16:409-17. 2003
    ..The role of FLT3 mutations in APL and other AML will be discussed...
  76. ncbi request reprint Genetics of myeloid leukemias
    Louise M Kelly
    Howard Hughes Medical Institute, Brigham and Women s Hospital, Harvard Institutes of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Genomics Hum Genet 3:179-98. 2002
    ..The data supporting this hypothesis and the clinical and therapeutic implications of these observations are reviewed...
  77. ncbi request reprint Genetics of myeloid malignancies: pathogenetic and clinical implications
    Stefan Fröhling
    Brigham and Women s Hospital, Division of Hematology, Karp Family Research Building, 5th Floor, 1 Blackfan Cir, Boston, MA 02115, USA
    J Clin Oncol 23:6285-95. 2005
    ..Specific examples discussed include RAS mutations, KIT mutations, FLT3 mutations, and core binding factor rearrangements in AML, and JAK2 mutations in polycythemia vera, essential thrombocytosis, and chronic idiopathic myelofibrosis...
  78. pmc PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model
    Louise M Kelly
    Division of Hematology Oncology, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:8283-8. 2002
    ..The leukemia is transplantable to secondary recipients and is ATRA responsive. These observations document cooperation between PML/RARalpha and FLT3-ITD in development of the murine APL phenotype...
  79. ncbi request reprint The Tel-Abl (ETV6-Abl) tyrosine kinase, product of complex (9;12) translocations in human leukemia, induces distinct myeloproliferative disease in mice
    Ryan P Million
    The Center for Blood Research and Department of Genetics, Brigham and Women s Hospital, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Blood 99:4568-77. 2002
    ..These results show that Tel-Abl has leukemogenic properties from distinct from those of Bcr-Abl and may act in a different bone marrow progenitor...
  80. ncbi request reprint A role for JAK2 mutations in myeloproliferative diseases
    Kelly J Morgan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Annu Rev Med 59:213-22. 2008
    ..Regardless of the various pathologies, the JAK2V617F discovery highlights the importance of JAK-STAT signaling in myeloid differentiation and focuses effort on developing a clinically relevant JAK2 inhibitor...
  81. ncbi request reprint Role of FLT3 in leukemia
    D Gary Gilliland
    Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA
    Curr Opin Hematol 9:274-81. 2002
    ..Collectively, these data indicate that FLT3 may be a viable therapeutic target for treatment of AML...
  82. ncbi request reprint JAK-2 mutations and their relevance to myeloproliferative disease
    Ross L Levine
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Curr Opin Hematol 14:43-7. 2007
    ..This review focuses on recent studies offering new genetic, biochemical, and functional insight into the role of JAK2V617F in the pathogenesis of these disorders...
  83. doi request reprint FoxO transcription factors and stem cell homeostasis: insights from the hematopoietic system
    Zuzana Tothova
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell Stem Cell 1:140-52. 2007
    ....
  84. ncbi request reprint Oncogenic K-ras in mouse models of myeloproliferative disease and acute myeloid leukemia
    Iris T Chan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Cell Cycle 3:536-7. 2004
    ..The model system with oncogenic K-ras provides a versatile platform to test the contribution of cooperating mutations in AML, and the efficacy of Ras pathway inhibitors in vivo...
  85. ncbi request reprint CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy
    Animesh Pardanani
    Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Blood 102:3093-6. 2003
    ..Screening for the FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance rational therapy decisions in SMCD...
  86. ncbi request reprint A model of APL with FLT3 mutation is responsive to retinoic acid and a receptor tyrosine kinase inhibitor, SU11657
    Jastinder Sohal
    Comprehensive Cancer Center and the Department of Laboratory Medicine, University of California, San Francisco, 94143, USA
    Blood 101:3188-97. 2003
    ..Our findings also indicate that APL patients with FLT3 mutations may benefit from combination therapy with all-trans retinoic acid plus an FLT3 inhibitor...
  87. ncbi request reprint The protein tyrosine kinase inhibitor SU5614 inhibits FLT3 and induces growth arrest and apoptosis in AML-derived cell lines expressing a constitutively activated FLT3
    Karsten Spiekermann
    Department of Medicine III, University Hospital Grosshadern, Clinical Cooperative Group Leukemia, GSF National Research Center for Environment and Health, Munich, Germany
    Blood 101:1494-504. 2003
    ..The selective and potent cytotoxicity of FLT3 PTK inhibitors support a clinical strategy of targeting FLT3 as a new molecular treatment option for patients with FLT3-LM/TKD-mutation(+) AML...
  88. ncbi request reprint Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness
    Amy D Klion
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 101:4660-6. 2003
    ..In summary, elevated serum tryptase appears to be a sensitive marker of a myeloproliferative variant of HES that is characterized by tissue fibrosis, poor prognosis, and imatinib responsiveness...
  89. pmc FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway
    Sumin Kang
    Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cancer Cell 12:201-14. 2007
    ..Our findings suggest that FGFR3 mediates hematopoietic transformation by activating RSK2 in a two-step fashion, promoting both the ERK-RSK2 interaction and subsequent phosphorylation of RSK2 by ERK...
  90. ncbi request reprint Jak2: normal function and role in hematopoietic disorders
    James N Ihle
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Curr Opin Genet Dev 17:8-14. 2007
    ..Recent studies have implicated de-regulation of Jak2 kinase activity by chromosomal translocations in hematopoietic tumors and mutations within the pseudokinase domain in a spectrum of myeloproliferative diseases...
  91. pmc Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation
    Xiaohui Lu
    Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 102:18962-7. 2005
    ..Our results reveal the molecular basis for the prevalence of JAK2V617F in diseases of myeloid lineage cells that express these Type I cytokine receptors but not in lymphoid lineage cells that do not...
  92. ncbi request reprint Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2(V617F) in granulocytes
    Terra L Lasho
    Br J Haematol 130:797-9. 2005
  93. ncbi request reprint Cancer biology: summing up cancer stem cells
    Brian J P Huntly
    Nature 435:1169-70. 2005
  94. pmc Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation
    Jason Gotlib
    Department of Medicine, Division of Hematology, Stanford University, Stanford Cancer Center, 875 Blake Wilbur Dr, Rm 2327B, Stanford, CA 94305 5821, USA
    Blood 106:2865-70. 2005
    ..This case indicates that KIT tyrosine kinase inhibition is a feasible approach in SM, but single-agent clinical efficacy may be limited by clonal evolution in the advanced leukemic phase of this disease...
  95. ncbi request reprint JAK2 in myeloproliferative disorders is not just another kinase
    Ayalew Tefferi
    Division of Hematology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Cell Cycle 4:1053-6. 2005
    ..Taken together, these observations suggest that JAK2(V617F) is an acquired myeloid lineage-specific mutation that engenders a pathogenetic relevance for the PV phenotype in MPD...
  96. pmc The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes
    David P Steensma
    Mayo Clinic and Mayo Clinic College of Medicine, Rochester MN 55905, USA
    Blood 106:1207-9. 2005
    ..The current observation strengthens the specific association between JAK2 V617F and classic MPD, but also suggests an infrequent occurrence in other myeloid disorders...
  97. ncbi request reprint Global effects of BCR/ABL and TEL/PDGFRbeta expression on the proteome and phosphoproteome: identification of the Rho pathway as a target of BCR/ABL
    Richard D Unwin
    Faculty of Medical and Human Sciences, University of Manchester
    J Biol Chem 280:6316-26. 2005
    ..Expression of a dominant-negative RhoA inhibited both DNA synthesis and transwell migration, demonstrating the significance of this pathway in BCR/ABL-mediated transformation...
  98. pmc A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia
    Ting Lei Gu
    Cell Signaling Technology, Danvers, MA 01923, USA
    Blood 110:323-33. 2007
    ..These findings identify a novel potential therapeutic target in leukemogenesis, and demonstrate the utility of phosphoproteomic strategies for discovery of tyrosine kinase alleles...