AF9

Summary

Gene Symbol: AF9
Description: MLLT3, super elongation complex subunit
Alias: AF9, YEATS3, protein AF-9, ALL1-fused gene from chromosome 9 protein, YEATS domain-containing protein 3, myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog); translocated to, 3, myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3, myeloid/lymphoid or mixed-lineage leukemia translocated to chromosome 3 protein, myeloid/lymphoid or mixed-lineage leukemia; translocated to 3
Species: human
Products:     AF9

Top Publications

  1. Wei J, Wunderlich M, Fox C, Alvarez S, Cigudosa J, Wilhelm J, et al. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell. 2008;13:483-95 pubmed publisher
    ..We show that expression of MLL-AF9 in human CD34+ cells induces acute myeloid, lymphoid, or mixed-lineage leukemia in immunodeficient mice...
  2. Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, et al. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci U S A. 1993;90:4631-5 pubmed
    ..Stretches abundant in basic amino acids are also present in the three proteins. These results suggest that the different proteins fused to ALL-1 polypeptide(s) provide similar functional domains. ..
  3. Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary M. A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell. 2010;17:198-212 pubmed publisher
    ..Thus, AEP recruitment is an integral part of both physiological and pathological MLL-dependent transcriptional pathways. Bypass of its normal recruitment mechanisms is the strategy most frequently used by MLL oncoproteins. ..
  4. He N, Chan C, Sobhian B, Chou S, Xue Y, Liu M, et al. Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin. Proc Natl Acad Sci U S A. 2011;108:E636-45 pubmed publisher
    ..Complex (SEC), containing transcription elongation activators/coactivators P-TEFb, ELL2, AFF4/1, ENL, and AF9, is recruited by HIV-1 Tat and mixed lineage leukemia (MLL) proteins to activate the expression of HIV-1 and MLL-..
  5. Iida S, Seto M, Yamamoto K, Komatsu H, Tojo A, Asano S, et al. MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13. Oncogene. 1993;8:3085-92 pubmed
    ..As previously found in t(11;19) leukemia, heterogeneous MLL-MLLT3 chimeric mRNAs could be detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) in t(9;11) leukemia samples. ..
  6. Srinivasan R, de Erkenez A, Hemenway C. The mixed lineage leukemia fusion partner AF9 binds specific isoforms of the BCL-6 corepressor. Oncogene. 2003;22:3395-406 pubmed
    ..Evidence suggests that the resulting MLL fusion genes contribute to leukemogenesis. AF9 is a common MLL fusion partner in acute myeloid leukemia...
  7. Sobhian B, Laguette N, Yatim A, Nakamura M, Levy Y, Kiernan R, et al. HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. Mol Cell. 2010;38:439-51 pubmed publisher
    ..Tatcom1 consists of the core active P-TEFb, MLL-fusion partners involved in leukemia (AF9, AFF4, AFF1, ENL, and ELL), and PAF1 complex...
  8. He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, et al. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell. 2010;38:428-38 pubmed publisher
    ..a sequential affinity-purification scheme, we have identified human transcription factors/coactivators AFF4, ENL, AF9, and elongation factor ELL2 as components of the Tat-P-TEFb complex...
  9. Jayavelu A, Müller J, Bauer R, Böhmer S, Lässig J, Cerny Reiterer S, et al. NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells. Leukemia. 2016;30:473-83 pubmed publisher
    ..by FLT3ITD-transformed 32D cells in C3H/HeJ mice, and of a leukemia-like disease in mice transplanted with MLL-AF9/ FLT3ITD-transformed murine hematopoietic stem cells were strongly attenuated by NOX4 downregulation...

More Information

Publications125 found, 100 shown here

  1. Wang Y, Skibbe J, Hu C, Dong L, Ferchen K, Su R, et al. ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged leukemia. Sci Rep. 2017;7:1853 pubmed publisher
    ..Stat and K-Ras signaling pathways were negatively correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells; inhibition of the above signaling pathways mimicked the drug-sensitizing effect of ALOX5 in ..
  2. Afrin S, Zhang C, Meyer C, Stinson C, Pham T, Bruxner T, et al. Targeted Next-Generation Sequencing for Detecting MLL Gene Fusions in Leukemia. Mol Cancer Res. 2018;16:279-285 pubmed publisher
    ..Furthermore, this assay rapidly and reliably identifies MLL partner genes and patient-specific fusion sequences that could be used for monitoring minimal residual disease. Mol Cancer Res; 16(2); 279-85. ©2017 AACR. ..
  3. Roychoudhury J, Clark J, Gracia Maldonado G, Unnisa Z, Wunderlich M, Link K, et al. MEIS1 regulates an HLF-oxidative stress axis in MLL-fusion gene leukemia. Blood. 2015;125:2544-52 pubmed publisher
    ..Here, we used inducible Meis1-knockout mice coupled with MLL-AF9 knockin mice to decipher the mechanistic role of Meis1 in established MLL leukemia...
  4. Kobayashi S, Obata M, Hagihara M, Motohashi K, Ito S, Ohshima R, et al. The presence of mature granulocytes/monocytes derived from leukemic cells in MLL-associated leukemia. Int J Hematol. 2009;90:591-596 pubmed publisher
    ..MLL partner genes were AF6, AF9, ELL, and ENL, respectively...
  5. Long J, Fang W, Chang L, Gao W, Shen Y, Jia M, et al. Targeting HDAC3, a new partner protein of AKT in the reversal of chemoresistance in acute myeloid leukemia via DNA damage response. Leukemia. 2017;31:2761-2770 pubmed publisher
    ..Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9+ leukemia to chemotherapy...
  6. Xu B, On D, Ma A, Parton T, Konze K, Pattenden S, et al. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood. 2015;125:346-57 pubmed publisher
    ..Oral administration of UNC1999 prolongs survival of a well-defined murine leukemia model bearing MLL-AF9. Collectively, our study provides the detailed profiling for a set of chemicals to manipulate EZH2 and EZH1 and ..
  7. Mar B, Chu S, Kahn J, Krivtsov A, Koche R, Castellano C, et al. SETD2 alterations impair DNA damage recognition and lead to resistance to chemotherapy in leukemia. Blood. 2017;130:2631-2641 pubmed publisher
    ..Heterozygous conditional inactivation of Setd2 in a murine model decreased the latency of MLL-AF9-induced leukemia and caused resistance to cytarabine treatment in vivo, whereas homozygous loss delayed leukemia ..
  8. Hossain M, Xie L, Caywood E. Prognostic factors of childhood and adolescent acute myeloid leukemia (AML) survival: evidence from four decades of US population data. Cancer Epidemiol. 2015;39:720-6 pubmed publisher
    ..Contrary to previous findings, the subtypes of AML with t(9;11)(p22;q23)MLLT3-MLL, AML without maturation and acute myelomonocytic leukemia emerged to be indicative of poor outcome. ..
  9. Pasini D, Malatesta M, Jung H, Walfridsson J, Willer A, Olsson L, et al. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res. 2010;38:4958-69 pubmed publisher
    ..correlates with the transcriptional activation of PcG target genes, both during ES cell differentiation and in MLL-AF9-transduced hematopoietic stem cells...
  10. Li H, Mar B, Zhang H, Puram R, Vazquez F, Weir B, et al. The EMT regulator ZEB2 is a novel dependency of human and murine acute myeloid leukemia. Blood. 2017;129:497-508 pubmed publisher
    ..observed in human cell lines, we performed a secondary screen in a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein...
  11. Gao S, Zhou B, Li H, Huang X, Wu Y, Xing C, et al. Long noncoding RNA HOTAIR promotes the self-renewal of leukemia stem cells through epigenetic silencing of p15. Exp Hematol. 2018;67:32-40.e3 pubmed publisher
    ..reduced infiltration of leukemic blasts, decreased frequency of LSC, and prolonged overall survival in MLL-AF9-induced murine leukemia, suggesting that HOTAIR is required for the maintenance of AML...
  12. Schulze I, Rohde C, Scheller Wendorff M, Bäumer N, Krause A, Herbst F, et al. Increased DNA methylation of Dnmt3b targets impairs leukemogenesis. Blood. 2016;127:1575-86 pubmed publisher
    ..MLL-AF9-induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression...
  13. Saito Y, Chapple R, Lin A, Kitano A, Nakada D. AMPK Protects Leukemia-Initiating Cells in Myeloid Leukemias from Metabolic Stress in the Bone Marrow. Cell Stem Cell. 2015;17:585-96 pubmed publisher
    ..Upon dietary restriction, MLL-AF9-induced murine acute myeloid leukemia (AML) activated AMPK and maintained leukemogenic potential...
  14. Bahr C, von Paleske L, Uslu V, Remeseiro S, Takayama N, Ng S, et al. A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies. Nature. 2018;553:515-520 pubmed publisher
    ..We show that BENC is also essential for the maintenance of MLL-AF9-driven leukaemia in mice...
  15. Zhang H, Zhang N, Wang R, Shao T, Feng Y, Yao Y, et al. High expression of miR-363 predicts poor prognosis and guides treatment selection in acute myeloid leukemia. J Transl Med. 2019;17:106 pubmed publisher
    ..AML patients with high miR-363 expression may be highly recommended for early allo-HSCT regimen. ..
  16. Kang X, Cui C, Wang C, Wu G, Chen H, Lu Z, et al. CAMKs support development of acute myeloid leukemia. J Hematol Oncol. 2018;11:30 pubmed publisher
    ..activation of CAMKs, and the forced expression of CAMK partially rescued the PirB-defective phenotype in the MLL-AF9 AML mouse model...
  17. Khalaj M, Woolthuis C, Hu W, Durham B, Chu S, Qamar S, et al. miR-99 regulates normal and malignant hematopoietic stem cell self-renewal. J Exp Med. 2017;: pubmed publisher
    ..Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary ..
  18. Chen Y, Jones K, Anastassiadis K, Kranz A, Stewart A, Grembecka J, et al. Distinct pathways affected by menin versus MLL1/MLL2 in MLL-rearranged acute myeloid leukemia. Exp Hematol. 2019;69:37-42 pubmed publisher
    ..We show that Men1 deletion in MLL-AF9-transformed leukemia cells produces distinct cellular and molecular consequences compared with Mll1;Mll2 co-..
  19. Dawson M, Prinjha R, Dittmann A, Giotopoulos G, Bantscheff M, Chan W, et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011;478:529-33 pubmed publisher
    ..I-BET151 has significant therapeutic value, providing survival benefit in two distinct mouse models of murine MLL-AF9 and human MLL-AF4 leukaemia...
  20. Zhang J, Ramadan A, Griesenauer B, Li W, Turner M, Liu C, et al. ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease. Sci Transl Med. 2015;7:308ra160 pubmed publisher
    ..ST2 blockade preserved graft-versus-leukemia activity in a model of green fluorescent protein (GFP)-positive MLL-AF9 acute myeloid leukemia...
  21. Ney Garcia D, de Souza M, de Figueiredo A, Othman M, Rittscher K, Abdelhay E, et al. Molecular characterization of KMT2A fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes. Hematol Oncol. 2016;: pubmed publisher
    ..We conclude that the combination of molecular techniques used in this study can efficiently identify KMT2A fusion partners in complex pediatric acute leukemia karyotypes. Copyright © 2016 John Wiley & Sons, Ltd. ..
  22. Hönes J, Botezatu L, Helness A, Vadnais C, Vassen L, Robert F, et al. GFI1 as a novel prognostic and therapeutic factor for AML/MDS. Leukemia. 2016;30:1237-45 pubmed publisher
    ..Here we show that AML development induced by onco-fusion proteins such as MLL-AF9 or NUP98-HOXD13 is accelerated in mice with low human GFI1 expression...
  23. Hsu C, Zhao D, Shi J, Peng D, Guan H, Li Y, et al. Gas41 links histone acetylation to H2A.Z deposition and maintenance of embryonic stem cell identity. Cell Discov. 2018;4:28 pubmed publisher
    ..The crystal structure of the Gas41 YEATS domain in complex with the H3K27ac peptide revealed that, similar to the AF9 and ENL YEATS domains, Gas41 YEATS forms a serine-lined aromatic cage for acetyllysine recognition...
  24. Zhou B, Wang J, Lee S, Xiong J, Bhanu N, Guo Q, et al. PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity. Mol Cell. 2016;62:222-236 pubmed publisher
    ..support of the tumor suppressor function of PRDM16, silencing PRDM16 by DNA methylation is concomitant with MLL-AF9-induced leukemic transformation...
  25. Guo H, Chu Y, Wang L, Chen X, Chen Y, Cheng H, et al. PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia. Int J Cancer. 2017;141:324-335 pubmed publisher
    ..Pbx3 in AML maintenance and progression, we used the CRISPR/Cas9 system to delete Pbx3 in leukemic cells in the MLL-AF9 induced AML mouse model...
  26. Bäumer N, Bäumer S, Berkenfeld F, Stehling M, Köhler G, Berdel W, et al. Maintenance of leukemia-initiating cells is regulated by the CDK inhibitor Inca1. PLoS ONE. 2014;9:e115578 pubmed publisher
    ..The re-initiation of leukemia was also significantly inhibited in absence of Inca1-/- in MLL-AF9- and c-myc/BCL2-positive leukemia mouse models...
  27. Sánchez Aguilera A, Arranz L, Martín Pérez D, García García A, Stavropoulou V, Kubovcakova L, et al. Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis. Cell Stem Cell. 2014;15:791-804 pubmed publisher
    ..neoplasm in vivo, induced apoptosis of human JAK2(V617F+) HSPCs in a xenograft model, and sensitized MLL-AF9(+) leukemias to chemotherapy...
  28. Gong Y, Zhao M, Yang W, Gao A, Yin X, Hu L, et al. Megakaryocyte-derived excessive transforming growth factor β1 inhibits proliferation of normal hematopoietic stem cells in acute myeloid leukemia. Exp Hematol. 2018;60:40-46.e2 pubmed publisher
    ..that transforming growth factor β (TGFβ) signaling was upregulated in HSCs from bone marrow of mice with MLL-AF9-induced acute myeloid leukemia (AML) because of excessive production of TGFβ1, especially from megakaryocytes, and ..
  29. Wai D, Szyszka T, Campbell A, Kwong C, Wilkinson White L, Silva A, et al. The BRD3 ET domain recognizes a short peptide motif through a mechanism that is conserved across chromatin remodelers and transcriptional regulators. J Biol Chem. 2018;293:7160-7175 pubmed publisher
    ..NMR-based structural analysis revealed that, surprisingly, this mode of interaction is shared by the AF9 and ENL transcriptional coregulators that contain an acetyl-lysine-binding YEATS domain and regulate ..
  30. Ye M, Zhang H, Yang H, Koche R, Staber P, Cusan M, et al. Hematopoietic Differentiation Is Required for Initiation of Acute Myeloid Leukemia. Cell Stem Cell. 2015;17:611-23 pubmed publisher
    ..Using murine MLL-AF9 and MOZ-TIF2 AML models, we show that myeloid differentiation to granulocyte macrophage progenitors (GMPs) is ..
  31. Stubbs M, Krivtsov A. Murine Retrovirally-Transduced Bone Marrow Engraftment Models of MLL-Fusion-Driven Acute Myelogenous Leukemias (AML). Curr Protoc Pharmacol. 2017;78:14.42.1-14.42.19 pubmed publisher
    ..The protocols detailed in this unit focus on bone marrow-derived models only, using one particular MLL fusion, MLL-AF9. These models have proven effective for drug screening to predict clinical response...
  32. Willer A, Jakobsen J, Ohlsson E, Rapin N, Waage J, Billing M, et al. TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia. Leukemia. 2015;29:1018-31 pubmed publisher
    ..blasts demonstrated reduced TGIF1 levels, and, in accordance, we find that forced expression of TGIF1 in MLL-AF9-transformed cells promoted differentiation and cell cycle exit in vitro, and delayed leukemic onset in vivo...
  33. Skucha A, Ebner J, Schmöllerl J, Roth M, Eder T, César Razquin A, et al. MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. Nat Commun. 2018;9:1983 pubmed publisher
    ..In addition to its role in H3K36 tri-methylation, SETD2 is required to maintain high H3K79 di-methylation and MLL-AF9-binding to critical target genes, such as Hoxa9...
  34. Minzel W, Venkatachalam A, Fink A, Hung E, Brachya G, Burstain I, et al. Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. Cell. 2018;175:171-185.e25 pubmed publisher
    ..their therapeutic efficacy with preserved hematopoiesis and leukemia cure potential; they eradicate leukemia in MLL-AF9 and Tet2-/-;Flt3ITD AML mouse models and in several patient-derived AML xenograft models, ..
  35. Konop C, Knickelbine J, Sygulla M, Vestling M, Stretton A. Different neuropeptides are expressed in different functional subsets of cholinergic excitatory motorneurons in the nematode Ascaris suum. ACS Chem Neurosci. 2015;6:855-70 pubmed publisher
    ..Strikingly, the two sets of neurons contain different neuropeptides, with AF9 and six novel peptides (As-NLP-21...
  36. Mian Y, Zeleznik Le N. The miR-17∼92 cluster contributes to MLL leukemia through the repression of MEIS1 competitor PKNOX1. Leuk Res. 2016;46:51-60 pubmed publisher
    ..MEIS1 in PBX-containing complex formation and determine the antagonistic role of PKNOX1 to leukemia in a murine MLL-AF9 model...
  37. Pikman Y, Puissant A, Alexe G, Furman A, Chen L, Frumm S, et al. Targeting MTHFD2 in acute myeloid leukemia. J Exp Med. 2016;213:1285-306 pubmed publisher
    ..In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival...
  38. Kumar B, Kalvala A, Chu S, Rosen S, Forman S, Marcucci G, et al. Antileukemic activity and cellular effects of the antimalarial agent artesunate in acute myeloid leukemia. Leuk Res. 2017;59:124-135 pubmed publisher
    ..activity of ARTS was further confirmed in MV4-11 and FLT3-ITD+ primary AML cell xenografts as well as MLL-AF9 syngeneic murine AML model where ARTS treatment resulted in significant survival prolongation of treated mice ..
  39. Acevedo Sáenz L, Carmona Pérez L, Velilla Hernández P, Delgado J, Rugeles L M. The APPEESFRS Peptide, Restricted by the HLA-B*35:01 Molecule, and the APPEESFRF Variant Derived from an Autologous HIV-1 Strain Induces Polyfunctional Responses in CD8+ T Cells. Biores Open Access. 2015;4:115-20 pubmed publisher
    ..and maturation phenotype of CD8+ T-cells targeting the consensus APPEESFRS (AS9) epitope and its variant APPEESFRF (AF9), previously identified...
  40. Fleischmann K, Pagel P, von Frowein J, Magg T, Roscher A, Schmid I. The leukemogenic fusion gene MLL-AF9 alters microRNA expression pattern and inhibits monoblastic differentiation via miR-511 repression. J Exp Clin Cancer Res. 2016;35:9 pubmed publisher
    In this study we explored the role of microRNAs (miRNAs) as mediators of leukemogenic effects of the fusion gene MLL-AF9, which results from a frequent chromosomal translocation in infant and monoblastic acute myeloid leukemia (AML)...
  41. Li Z, Chen P, Su R, Hu C, Li Y, Elkahloun A, et al. PBX3 and MEIS1 Cooperate in Hematopoietic Cells to Drive Acute Myeloid Leukemias Characterized by a Core Transcriptome of the MLL-Rearranged Disease. Cancer Res. 2016;76:619-29 pubmed publisher
    ..overexpression also caused AML in vivo, with a leukemic latency similar to that caused by forced expression of MLL-AF9, the most common form of MLL fusions...
  42. Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, et al. miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism. Blood. 2017;129:1491-1502 pubmed publisher
    ..overexpression and MLL translocations by examining functional cooperation between miR-125b and MLL-AF9 By generating a knock-in mouse model in which miR-125b overexpression is controlled by doxycycline ..
  43. Zhang F, Liu X, Chen C, Zhu J, Yu Z, Xie J, et al. CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27kip1 signaling. Haematologica. 2017;102:707-718 pubmed publisher
    ..Using an MLL-AF9-induced murine acute myeloid leukemia model, we show that leukemogenesis is dramatically delayed upon CD244 ..
  44. Wan L, Wen H, Li Y, Lyu J, Xi Y, Hoshii T, et al. ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia. Nature. 2017;543:265-269 pubmed publisher
    ..Here we show that the YEATS domain-containing protein ENL, but not its paralogue AF9, is required for disease maintenance in acute myeloid leukaemia...
  45. Wang Y, Chen C, Dong F, Ma S, Xu J, Gong Y, et al. NK cells play a significant role in immunosurveillance at the early stage of MLL-AF9 acute myeloid leukemia via CD226/CD155 interactions. Sci China Life Sci. 2015;58:1288-98 pubmed publisher
    ..In the present study, we utilized a myeloid/lymphoid or mixed-lineage leukemia; translocated to, 3 (MLLT3/MLL-AF9)-induced AML mouse model with or without exposure to irradiation...
  46. Vukovic M, Guitart A, Sepúlveda C, Villacreces A, O Duibhir E, Panagopoulou T, et al. Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance. J Exp Med. 2015;212:2223-34 pubmed publisher
    ..of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9...
  47. Ghisi M, Kats L, Masson F, Li J, Kratina T, Vidacs E, et al. Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell. 2016;30:59-74 pubmed publisher
    ..Low endogenous Id2 expression is associated with LSC enrichment while Id2 overexpression impairs MLL-AF9-leukemia initiation and growth...
  48. Watanabe T, Ernst P. Context, Context, Context: New Gene Programs Linked to Bad Behavior in MLL-AF9-Initiated Leukemia. Cancer Cell. 2016;30:3-5 pubmed publisher
    In this issue of Cancer Cell, Stavropoulou et al. report that expression of the MLL-AF9 fusion results in acute myelogenous leukemia (AML) with different behaviors depending on cell context, which leads them to identify a ..
  49. Cui P, Zhang Y, Cui M, Li Z, Ma G, Wang R, et al. Leukemia cells impair normal hematopoiesis and induce functionally loss of hematopoietic stem cells through immune cells and inflammation. Leuk Res. 2018;65:49-54 pubmed publisher
    ..In the present study, we utilized one of the most frequent leukemogenic translocations MLL-AF9 to induce leukemia and investigated the hematopoiesis and the activity of hematopoietic stem and progenitor cells (..
  50. Sarashina T, Iwabuchi H, Miyagawa N, Sekimizu M, Yokosuka T, Fukuda K, et al. Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature. Int J Hematol. 2016;104:139-43 pubmed publisher
    ..However, rare cases of mature B-ALL with non-L3 morphology and MLL-AF9 fusion have been reported, and such cases are characterized by a rapid and aggressive clinical course...
  51. Valerio D, Xu H, Chen C, Hoshii T, Eisold M, Delaney C, et al. Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis. Cancer Res. 2017;77:1753-1762 pubmed publisher
    ..Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival...
  52. Charmsaz S, Beckett K, Smith F, Bruedigam C, Moore A, Al Ejeh F, et al. EphA2 Is a Therapy Target in EphA2-Positive Leukemias but Is Not Essential for Normal Hematopoiesis or Leukemia. PLoS ONE. 2015;10:e0130692 pubmed publisher
    ..Comparative studies using EphA2-negative MLL-AF9 leukemias derived from EphA2-knockout animals showed that there was no detectable functional role for EphA2 in the ..
  53. Agger K, Miyagi S, Pedersen M, Kooistra S, Johansen J, Helin K. Jmjd2/Kdm4 demethylases are required for expression of Il3ra and survival of acute myeloid leukemia cells. Genes Dev. 2016;30:1278-88 pubmed publisher
    ..the feasibility of using the H3K9- and H3K36-specific demethylases Jmjd2/Kdm4 as putative drug targets in MLL-AF9 translocated leukemia...
  54. Germano G, Morello G, Aveic S, Pinazza M, Minuzzo S, Frasson C, et al. ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid leukemia. Oncotarget. 2017;8:26129-26141 pubmed publisher
    ..In this study, we sought to analyze the effect of ZNF521 depletion on MLL-rearranged AML cell lines and MLL-AF9 xenograft primary cells...
  55. Taube R, Peterlin M. Lost in transcription: molecular mechanisms that control HIV latency. Viruses. 2013;5:902-27 pubmed publisher
  56. Lin S, Luo R, Ptasinska A, Kerry J, Assi S, Wunderlich M, et al. Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia. Cancer Cell. 2016;30:737-749 pubmed publisher
    ..MLL-Af4 induces a B ALL distinct from MLL-AF9 through differential genomic target binding of the fusion proteins leading to specific gene expression patterns...
  57. Fang X, Chen C, Xia F, Yu Z, Zhang Y, Zhang F, et al. CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling. J Hematol Oncol. 2016;9:124 pubmed
    ..However, the role of CD274 in leukemia-initiating cells (LICs) remains largely unknown. We established an MLL-AF9-induced acute myeloid leukemia (AML) model with wild-type (WT) and CD274-null mice to elucidate the role of CD274 ..
  58. Capela de Matos R, Ney Garcia D, Cifoni E, Othman M, Tavares de Souza M, Carboni E, et al. GAS6 Oncogene and Reverse MLLT3-KMT2A Duplications in an Infant with Acute Myeloid Leukemia and a Novel Complex Hyperdiploid Karyotype: Detailed High-Resolution Molecular Cytogenetic Studies. Cytogenet Genome Res. 2017;152:33-37 pubmed publisher
    ..Our work suggests that molecular cytogenetic studies are crucial for the planning of a proper strategy for risk therapy in AML infants with hyperdiploid karyotypes. ..
  59. Cheng H, Hao S, Liu Y, Pang Y, Ma S, Dong F, et al. Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation. Blood. 2015;126:1302-13 pubmed publisher
    ..To investigate these important questions, we used a robust nonirradiated mouse model of human MLL-AF9 leukemia to examine the suppression of HSCs and HPCs during leukemia cell expansion in vivo...
  60. Fong C, Gilan O, Lam E, Rubin A, Ftouni S, Tyler D, et al. BET inhibitor resistance emerges from leukaemia stem cells. Nature. 2015;525:538-42 pubmed publisher
    ..Here we use primary mouse haematopoietic stem and progenitor cells immortalized with the fusion protein MLL-AF9 to generate several single-cell clones that demonstrate resistance, in vitro and in vivo, to the prototypical BET ..
  61. Cole C, Verdoni A, Ketkar S, Leight E, Russler Germain D, Lamprecht T, et al. PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia. J Clin Invest. 2016;126:85-98 pubmed publisher
    ..in AML patients with translocations that create oncogenic fusion genes such as PML-RARA, RUNX1-RUNX1T1, and MLL-AF9. Here, we explored how DNMT3A is involved in the function of these fusion genes...
  62. Eckfeldt C, Pomeroy E, Lee R, Hazen K, Lee L, Moriarity B, et al. RALB provides critical survival signals downstream of Ras in acute myeloid leukemia. Oncotarget. 2016;7:65147-65156 pubmed publisher
    ..Whereas genetic disruption of NRAS(V12) expression in an NRAS(V12) and Mll-AF9-driven murine AML induced apoptosis of leukemic cells, inhibition of phosphatidylinositol-3-kinase (PI3K) and/or ..
  63. Carretta M, de Boer B, Jaques J, Antonelli A, Horton S, Yuan H, et al. Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further improve human scaffold-based xenograft models. Exp Hematol. 2017;51:36-46 pubmed publisher
    ..MLL-AF9-transduced CB CD34+ cells could be transformed efficiently along myeloid or lymphoid lineages on IL-3- ..
  64. Di Marcantonio D, Martinez E, Sidoli S, Vadaketh J, Nieborowska Skorska M, Gupta A, et al. Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia. Clin Cancer Res. 2018;24:608-618 pubmed publisher
    ..AML cell survival as well as disease onset in a genetically engineered mouse model (GEMM) of AML driven by MLL-AF9. We also show that PKCε inhibition induces multiple reactive oxygen species (ROS) and that neutralization of ..
  65. Rathert P, Roth M, Neumann T, Muerdter F, Roe J, Muhar M, et al. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Nature. 2015;525:543-547 pubmed publisher
    ..and acquired BET resistance in leukaemia, here we perform a chromatin-focused RNAi screen in a sensitive MLL-AF9;Nras(G12D)-driven AML mouse model, and investigate dynamic transcriptional profiles in sensitive and resistant ..
  66. Thowfeik F, AbdulSalam S, Wunderlich M, Wyder M, Greis K, Kadekaro A, et al. A ROS-Activatable Agent Elicits Homologous Recombination DNA Repair and Synergizes with Pathway Compounds. Chembiochem. 2015;16:2513-21 pubmed publisher
    ..In this study, the mechanism of action and synergistic effects against cells coexpressing the AML oncogenes MLL-AF9 fusion and FLT3-ITD were investigated. One RAC (RAC1) had an IC50 value of 1.8±0...
  67. Zhao D, Li Y, Xiong X, Chen Z, Li H. YEATS Domain-A Histone Acylation Reader in Health and Disease. J Mol Biol. 2017;429:1994-2002 pubmed publisher
    ..The Yaf9, ENL, AF9, Taf14, Sas5 (YEATS) domain is an emerging reader module that selectively recognizes histone lysine acylation with ..
  68. Zhang Y, Xia F, Liu X, Yu Z, Xie L, Liu L, et al. JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/?-catenin/CCND1 signaling. J Clin Invest. 2018;128:1737-1751 pubmed publisher
    ..Leukemogenesis is almost completely abrogated upon Jam3 deletion during serial transplantations in an MLL-AF9-induced murine acute myeloid leukemia model...
  69. Mbonye U, Karn J. Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure. Virology. 2014;454-455:328-39 pubmed publisher
    ..An in-depth comprehensive understanding of the molecular control of HIV-1 transcription should inform the development of optimal combinatorial reactivation strategies that are intended to purge the latent viral reservoir...
  70. Martino V, Tonelli R, Montemurro L, Franzoni M, Marino F, Fazzina R, et al. Down-regulation of MLL-AF9, MLL and MYC expression is not obligatory for monocyte-macrophage maturation in AML-M5 cell lines carrying t(9;11)(p22;q23). Oncol Rep. 2006;15:207-11 pubmed
    The MLL-AF9 oncogene originates from the translocation t(9;11)(p22;q23), which is mainly associated with monocytic acute myeloid leukaemia (AML-M5; FAB-classification)...
  71. Barretto N, Karahalios D, You D, Hemenway C. An AF9/ENL-targted peptide with therapeutic potential in mixed lineage leukemias. J Exp Ther Oncol. 2014;10:293-300 pubmed
    Misregulation of transcription elongation is proposed to underlie the pathobiology of MLL leukemia. AF4, AF9, and ENL, common MLL fusion partners, are found in complex with positive transcription elongation factor b (P-TEFb)...
  72. Lin J, Hemenway C. Hsp90 directly modulates the spatial distribution of AF9/MLLT3 and affects target gene expression. J Biol Chem. 2010;285:11966-73 pubmed publisher
    b>AF9/MLLT3 contributes to the regulation of the gene encoding the epithelial sodium channel alpha, ENaCalpha, in renal tubular cells...
  73. Bergerson R, Collier L, Sarver A, Been R, Lugthart S, Diers M, et al. An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model. Blood. 2012;119:4512-23 pubmed publisher
    Patients with a t(9;11) translocation (MLL-AF9) develop acute myeloid leukemia (AML), and while in mice the expression of this fusion oncogene also results in the development of myeloid leukemia, it is with long latency...
  74. Montemurro L, Tonelli R, Fazzina R, Martino V, Marino F, Pession A. Identification of two MLL-MLLT3 (alias MLL-AF9) chimeric transcripts in the MOLM-13 cell line. Cancer Genet Cytogenet. 2004;154:96-7 pubmed
  75. Sugino N, Kawahara M, Tatsumi G, Kanai A, Matsui H, Yamamoto R, et al. A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers. Leukemia. 2017;31:2303-2314 pubmed publisher
    ..Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDSs) overt leukemia ..
  76. He J, Chen Z, Xue Y, Li J, He H, Huang Y, et al. [Detection of fusion genes resulting from chromosome abnormalities in childhood acute lymphoblastic leukemia]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005;22:551-3 pubmed
    ..with immunophenotype of Pre-B-ALL were found to carry: TEL/AML1(3 cases); E2A/PBX1, E2A/HLF, TLS/ERG, MLL/AF4, MLL/AF9, MLL/AF10, MLL/AFX-MLL/AF6-MLL/ELL, MLL/AF6-MLL/ELL, dupMLL (one case for each); and HOX11 (6 cases)...
  77. Monroe S, Jo S, Sanders D, Basrur V, Elenitoba Johnson K, Slany R, et al. MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia. Exp Hematol. 2011;39:77-86.e1-5 pubmed publisher
    ..The transforming domain of one of the most common MLL fusion partners, AF9, was immunopurified after expression in myeloblastic M1 cells, and associating proteins were identified by mass ..
  78. Huynh K, Fischle W, Verdin E, Bardwell V. BCoR, a novel corepressor involved in BCL-6 repression. Genes Dev. 2000;14:1810-23 pubmed
    ..Additionally, interactions between the BCL-6 POZ domain and SMRT, N-CoR, and BCoR are mutually exclusive. The specificity of the BCL-6/BCoR interaction suggests that BCoR may have a role in BCL-6-associated lymphomas. ..
  79. Prange K, Mandoli A, Kuznetsova T, Wang S, Sotoca A, Marneth A, et al. MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia. Oncogene. 2017;36:3346-3356 pubmed publisher
    ..In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 ..
  80. Müller Schmah C, Solari L, Weis R, Pfeifer D, Scheibenbogen C, Trepel M, et al. Immune response as a possible mechanism of long-lasting disease control in spontaneous remission of MLL/AF9-positive acute myeloid leukemia. Ann Hematol. 2012;91:27-32 pubmed publisher
    ..We describe the 10-year follow-up of a patient with MLL-AF9-positive AML (Müller et al...
  81. Karn J, Stoltzfus C. Transcriptional and posttranscriptional regulation of HIV-1 gene expression. Cold Spring Harb Perspect Med. 2012;2:a006916 pubmed publisher
    ..In cells that are not fully activated, limiting levels of Tat and Rev act as potent blocks to premature virus production. ..
  82. Benedikt A, Baltruschat S, Scholz B, Bursen A, Arrey T, Meyer B, et al. The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. Leukemia. 2011;25:135-44 pubmed publisher
    ..Thus, we propose that these two processes are key to trigger cellular reprogramming that leads to the onset of acute leukemia. ..
  83. Osaki H, Walf Vorderwülbecke V, Mangolini M, Zhao L, Horton S, Morrone G, et al. The AAA+ ATPase RUVBL2 is a critical mediator of MLL-AF9 oncogenesis. Leukemia. 2013;27:1461-8 pubmed publisher
    ..acute myeloid leukemia affect the 11q23 locus and give rise to mixed lineage leukemia (MLL) fusion genes, MLL-AF9 being the most prevalent. The MLL-AF9 fusion gene has been shown to induce leukemia in both mouse and human models...
  84. Danis E, Yamauchi T, Echanique K, Haladyna J, Kalkur R, Riedel S, et al. Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model. Exp Hematol. 2015;43:930-935.e6 pubmed publisher
    ..In leukemia mediated by the leukemogenic fusion MLL-AF9, complete ablation of canonical PRC2 function by genetic inactivation of the core component embryonic ectoderm ..
  85. Garcia Cuellar M, Zilles O, Schreiner S, Birke M, Winkler T, Slany R. The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human Polycomb 3. Oncogene. 2001;20:411-9 pubmed
    ..An internal region of hPc3 was responsible for binding to ENL. Finally, hPc3 binds to the C-terminus of AF9, another common MLL fusion partner...
  86. Reisenauer M, Anderson M, Huang L, Zhang Z, Zhou Q, Kone B, et al. AF17 competes with AF9 for binding to Dot1a to up-regulate transcription of epithelial Na+ channel alpha. J Biol Chem. 2009;284:35659-69 pubmed publisher
    We previously reported that Dot1a.AF9 complex represses transcription of the epithelial Na(+) channel subunit alpha (alpha-ENaC) gene in mouse inner medullary collecting duct mIMCD3 cells and mouse kidney...
  87. Leach B, Kuntimaddi A, Schmidt C, Cierpicki T, Johnson S, Bushweller J. Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding. Structure. 2013;21:176-183 pubmed publisher
    ..We show that the ANC1 homology domain (AHD) of AF9, one of the most common MLL translocation partners, is intrinsically disordered and recruits multiple transcription ..
  88. Malik B, Hemenway C. CBX8, a component of the Polycomb PRC1 complex, modulates DOT1L-mediated gene expression through AF9/MLLT3. FEBS Lett. 2013;587:3038-44 pubmed publisher
    b>AF9 is known to interact with multiple proteins including activators and repressors of transcription...
  89. Yao C, Kobayashi M, Chen S, NABINGER S, Gao R, Liu S, et al. Necdin modulates leukemia-initiating cell quiescence and chemotherapy response. Oncotarget. 2017;8:87607-87622 pubmed publisher
    ..In this study, we utilized two well-established murine models of human AML induced by MLL-AF9 or AML1-ETO9a to determine the role of Necdin in leukemogenesis...
  90. Wang Q, Zheng Q, Zhang H. Exploring the mechanism how AF9 recognizes and binds H3K9ac by molecular dynamics simulations and free energy calculations. Biopolymers. 2016;105:779-86 pubmed publisher
    ..b>AF9 is an important one in the YEATS family...
  91. Mizukawa B, O Brien E, Moreira D, Wunderlich M, Hochstetler C, Duan X, et al. The cell polarity determinant CDC42 controls division symmetry to block leukemia cell differentiation. Blood. 2017;130:1336-1346 pubmed publisher
    ..In a mouse model of AML, the loss of Cdc42 abrogates MLL-AF9-induced AML development...
  92. Peng L, Tang Y, Zhang Y, Guo S, Peng L, Ye L, et al. Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia. Leuk Lymphoma. 2017;:1-8 pubmed publisher
    ..Using an MLL-AF9 induced AML mouse model, we demonstrated that down modulating of SMC4 expression could prolong the survival time of ..