nach oben

International Journal of Hematology

Erschienen in:

01.04.2015 | Progress in Hematology

The RUNX1–PU.1 axis in the control of hematopoiesis

verfasst von: Maria Rosaria Imperato, Pierre Cauchy, Nadine Obier, Constanze Bonifer

Erschienen in: International Journal of Hematology | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

The differentiation from multipotent hematopoietic stem cells (HSC) to mature and functional blood cells requires the finely tuned regulation of gene expression at each stage of development. Specific transcription factors play a key role in this process as they modulate the expression of their target genes in an exquisitely lineage-specific manner. A large number of important transcriptional regulators have been identified which establish and maintain specific gene expression patterns during hematopoietic development. Hematopoiesis is therefore a paradigm for investigating how transcription factors function in mammalian cells, thanks also to the evolution of genome-wide and the next-generation sequencing technologies. In this review, we focus on the current knowledge of the biological and functional properties of the hematopoietic master regulator RUNX1 (also known as AML1, CBFA2, PEBP2aB) transcription factor and its main downstream target PU.1. We will outline their relationship in determining the fate of the myeloid lineage during normal stem cell development and under conditions when hematopoietic development is subverted by leukemic transformation.

Bonifer C, Bowen DT. Epigenetic mechanisms regulating normal and malignant haematopoiesis: new therapeutic targets for clinical medicine. Expert Rev Mol Med. 2010;12:e6.PubMedCrossRef

Thornell A, Hallberg B, Grundstrom T. Differential protein binding in lymphocytes to a sequence in the enhancer of the mouse retrovirus SL3-3. Mol Cell Biol. 1988;8:1625–37.PubMedCentralPubMed

Kamachi Y, Ogawa E, Asano M, Ishida S, Murakami Y, Satake M, Ito Y, Shigesada K. Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer. J Virol. 1990;64:4808–19.PubMedCentralPubMed

Boral AL, Okenquist SA, Lenz J. Identification of the SL3-3 virus enhancer core as a T-lymphoma cell-specific element. J Virol. 1989;63:76–84.PubMedCentralPubMed

Wang SW, Speck NA. Purification of core-binding factor, a protein that binds the conserved core site in murine leukemia virus enhancers. Mol Cell Biol. 1992;12:89–102.PubMedCentralPubMed

Wang S, Wang Q, Crute BE, Melnikova IN, Keller SR, Speck NA. Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. Mol Cell Biol. 1993;13:3324–39.PubMedCentralPubMed

Ogawa E, Inuzuka M, Maruyama M, Satake M, Naito-Fujimoto M, Ito Y, Shigesada K. Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Virology. 1993;194:314–31.PubMedCrossRef

Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M. t[8, 21] breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA. 1991;88:10431–4.PubMedCentralPubMedCrossRef

Daga A, Tighe JE, Calabi F. Leukaemia/Drosophila homology. Nature. 1992;356:484.PubMedCrossRef

10.

Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H. Identification of breakpoints in t[8, 21] acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood. 1992;80:1825–31.PubMed

11.

Meyers S, Downing JR, Hiebert SW. Identification of AML-1 and the [8, 21] translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein-protein interactions. Mol Cell Biol. 1993;13:6336–45.PubMedCentralPubMed

12.

Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L, Groner Y. AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics. 1994;23:425–32.PubMedCrossRef

13.

Ghozi MC, Bernstein Y, Negreanu V, Levanon D, Groner Y. Expression of the human acute myeloid leukemia gene AML1 is regulated by two promoter regions. Proc Natl Acad Sci USA. 1996;93:1935–40.PubMedCentralPubMedCrossRef

14.

Goyama S, Huang G, Kurokawa M, Mulloy JC. Posttranslational modifications of RUNX1 as potential anticancer targets. Oncogene. 2014. doi:10.1038/onc.2014.305.PubMedCentral

15.

Huang G, Zhang P, Hirai H, Elf S, Yan X, Chen Z, Koschmieder S, Okuno Y, Dayaram T, Growney JD, et al. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet. 2008;40:51–60.PubMedCrossRef

16.

Hoogenkamp M, Krysinska H, Ingram R, Huang G, Barlow R, Clarke D, Ebralidze A, Zhang P, Tagoh H, Cockerill PN, et al. The PU.1 locus is differentially regulated at the level of chromatin structure and noncoding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis. Mol Cell Biol. 2007;27:7425–38.PubMedCentralPubMedCrossRef

17.

Moreau-Gachelin F, Tavitian A, Tambourin P. Spi-1 is a putative oncogene in virally induced murine erythroleukaemias. Nature. 1988;331:277–80.PubMedCrossRef

18.

Klemsz MJ, McKercher SR, Celada A, Van Beveren C, Maki RA. The macrophage and B cell-specific transcription factor PU.1 is related to the ETS oncogene. Cell. 1990;61:113–24.PubMedCrossRef

19.

Karim FD, Urness LD, Thummel CS, Klemsz MJ, McKercher SR, Celada A, Van Beveren C, Maki RA, Gunther CV, Nye JA, et al. The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev. 1990;4:1451–3.PubMedCrossRef

20.

Kodandapani R, Pio F, Ni CZ, Piccialli G, Klemsz M, McKercher S, Maki RA, Ely KR. A new pattern for helix-turn-helix recognition revealed by the PU.1 ETS-domain-DNA complex. Nature. 1996;380:456–60.PubMedCrossRef

21.

Klemsz MJ, Maki RA. Activation of transcription by PU.1 requires both acidic and glutamine domains. Mol Cell Biol. 1996;16:390–7.PubMedCentralPubMed

22.

Pongubala JM, Van Beveren C, Nagulapalli S, Klemsz MJ, McKercher SR, Maki RA, Atchison ML. Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Science. 1993;259:1622–5.PubMedCrossRef

23.

DeVilbiss AW, Sanalkumar R, Johnson KD, Keles S, Bresnick EH. Hematopoietic transcriptional mechanisms: from locus-specific to genome-wide vantage points. Exp Hematol. 2014;42:618–29.PubMedCrossRef

24.

Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH, Speck NA. Disruption of the CBFA2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci USA. 1996;93:3444–9.PubMedCentralPubMedCrossRef

25.

Wang Q, Stacy T, Miller JD, Lewis AF, Gu TL, Huang X, Bushweller JH, Bories JC, Alt FW, Ryan G, et al. The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell. 1996;87:697–708.PubMedCrossRef

26.

Bresciani E, Carrington B, Wincovitch S, Jones M, Gore AV, Weinstein BM, Sood R, Liu PP. CBFbeta and RUNX1 are required at 2 different steps during the development of hematopoietic stem cells in zebrafish. Blood. 2014;124:70–8.PubMedCrossRef

27.

Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996;84:321–30.PubMedCrossRef

28.

Ichikawa M, Asai T, Saito T, Seo S, Yamazaki I, Yamagata T, Mitani K, Chiba S, Ogawa S, Kurokawa M, et al. AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat Med. 2004;10:299–304.PubMedCrossRef

29.

Putz G, Rosner A, Nuesslein I, Schmitz N, Buchholz F. AML1 deletion in adult mice causes splenomegaly and lymphomas. Oncogene. 2006;25:929–39.PubMedCrossRef

30.

Growney JD, Shigematsu H, Li Z, Lee BH, Adelsperger J, Rowan R, Curley DP, Kutok JL, Akashi K, Williams IR, et al. Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood. 2005;106:494–504.PubMedCentralPubMedCrossRef

31.

Chen MJ, Yokomizo T, Zeigler BM, Dzierzak E, Speck NA. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature. 2009;457:887–91.PubMedCentralPubMedCrossRef

32.

Ichikawa M, Goyama S, Asai T, Kawazu M, Nakagawa M, Takeshita M, Chiba S, Ogawa S, Kurokawa M. AML1/Runx1 negatively regulates quiescent hematopoietic stem cells in adult hematopoiesis. J Immunol. 2008;180:4402–8.PubMedCrossRef

33.

Scott EW, Simon MC, Anastasi J, Singh H. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science. 1994;265:1573–7.PubMedCrossRef

34.

McKercher SR, Torbett BE, Anderson KL, Henkel GW, Vestal DJ, Baribault H, Klemsz M, Feeney AJ, Wu GE, Paige CJ, et al. Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 1996;15:5647–58.PubMedCentralPubMed

35.

Wilkinson AC, Kawata VK, Schutte J, Gao X, Antoniou S, Baumann C, Woodhouse S, Hannah R, Tanaka Y, Swiers G, et al. Single-cell analyses of regulatory network perturbations using enhancer-targeting TALEs suggest novel roles for PU.1 during haematopoietic specification. Development. 2014;141:4018–30.PubMedCentralPubMedCrossRef

36.

Lancrin C, Mazan M, Stefanska M, Patel R, Lichtinger M, Costa G, Vargel O, Wilson NK, Moroy T, Bonifer C, et al. GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment. Blood. 2012;120:314–22.PubMedCrossRef

37.

Medvinsky A, Rybtsov S, Taoudi S. Embryonic origin of the adult hematopoietic system: advances and questions. Development. 2011;138:1017–31.PubMedCrossRef

38.

Medvinsky A, Dzierzak E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell. 1996;86:897–906.PubMedCrossRef

39.

Kissa K, Herbomel P. Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature. 2010;464:112–5.PubMedCrossRef

40.

Lancrin C, Sroczynska P, Stephenson C, Allen T, Kouskoff V, Lacaud G. The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage. Nature. 2009;457:892–5.PubMedCentralPubMedCrossRef

41.

Eilken HM, Nishikawa S, Schroeder T. Continuous single-cell imaging of blood generation from haemogenic endothelium. Nature. 2009;457:896–900.PubMedCrossRef

42.

Moignard V, Woodhouse S, Fisher J, Gottgens B. Transcriptional hierarchies regulating early blood cell development. Blood Cells Mol Dis. 2013;51:239–47.PubMedCrossRef

43.

Swiers G, Baumann C, O’Rourke J, Giannoulatou E, Taylor S, Joshi A, Moignard V, Pina C, Bee T, Kokkaliaris KD, et al. Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level. Nat Commun. 2013;4:2924.PubMedCentralPubMedCrossRef

44.

Lichtinger M, Ingram R, Hannah R, Muller D, Clarke D, Assi SA, Lie ALM, Noailles L, Vijayabaskar MS, Wu M, et al. RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis. EMBO J. 2012;31:4318–33.PubMedCentralPubMedCrossRef

45.

Staber PB, Zhang P, Ye M, Welner RS, Nombela-Arrieta C, Bach C, Kerenyi M, Bartholdy BA, Zhang H, Alberich-Jorda M, et al. Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells. Mol Cell. 2013;49:934–46.PubMedCentralPubMedCrossRef

46.

Hohaus S, Petrovick MS, Voso MT, Sun Z, Zhang DE, Tenen DG. PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene. Mol Cell Biol. 1995;15:5830–45.PubMedCentralPubMed

47.

Aikawa, Y., Katsumoto, T., Zhang, P., Shima, H., Shino, M., Terui, K., Ito, E., Ohno, H., Stanley, E.R., Singh, H. et al. (2010) PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med, 16, 580-585, 581p following 585.

48.

Rieger MA, Hoppe PS, Smejkal BM, Eitelhuber AC, Schroeder T. Hematopoietic cytokines can instruct lineage choice. Science. 2009;325:217–8.PubMedCrossRef

49.

Mossadegh-Keller N, Sarrazin S, Kandalla PK, Espinosa L, Stanley ER, Nutt SL, Moore J, Sieweke MH. M-CSF instructs myeloid lineage fate in single haematopoietic stem cells. Nature. 2013;497:239–43.PubMedCentralPubMedCrossRef

50.

Heath V, Suh HC, Holman M, Renn K, Gooya JM, Parkin S, Klarmann KD, Ortiz M, Johnson P, Keller J. C/EBPalpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo. Blood. 2004;104:1639–47.PubMedCrossRef

51.

Suh HC, Gooya J, Renn K, Friedman AD, Johnson PF, Keller JR. C/EBPalpha determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation. Blood. 2006;107:4308–16.PubMedCentralPubMedCrossRef

52.

Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG. Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci USA. 1997;94:569–74.PubMedCentralPubMedCrossRef

53.

Yeamans C, Wang D, Paz-Priel I, Torbett BE, Tenen DG, Friedman AD. C/EBPalpha binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment. Blood. 2007;110:3136–42.PubMedCentralPubMedCrossRef

54.

Kueh HY, Champhekar A, Nutt SL, Elowitz MB, Rothenberg EV. Positive feedback between PU.1 and the cell cycle controls myeloid differentiation. Science. 2013;341:670–3.PubMedCentralPubMedCrossRef

55.

Hu Z, Gu X, Baraoidan K, Ibanez V, Sharma A, Kadkol S, Munker R, Ackerman S, Nucifora G, Saunthararajah Y. RUNX1 regulates corepressor interactions of PU.1. Blood. 2011;117:6498–508.PubMedCentralPubMedCrossRef

56.

Zhang DE, Hetherington CJ, Meyers S, Rhoades KL, Larson CJ, Chen HM, Hiebert SW, Tenen DG. CCAAT enhancer-binding protein (C/EBP) and AML1 (CBF alpha2) synergistically activate the macrophage colony-stimulating factor receptor promoter. Mol Cell Biol. 1996;16:1231–40.PubMedCentralPubMed

57.

Nakajima H, Asai A, Okada A, Ping L, Hamajima F, Sata T, Isobe K. Transcriptional regulation of ILT family receptors. J Immunol. 2003;171:6611–20.PubMedCrossRef

58.

Yu M, Mazor T, Huang H, Huang HT, Kathrein KL, Woo AJ, Chouinard CR, Labadorf A, Akie TE, Moran TB, et al. Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell. 2012;45:330–43.PubMedCentralPubMedCrossRef

59.

Gu X, Hu Z, Ebrahem Q, Crabb JS, Mahfouz RZ, Radivoyevitch T, Crabb JW, Saunthararajah Y. Runx1 regulation of PU.1 corepressor/coactivator exchange identifies specific molecular targets for leukemia differentiation therapy. J Biol Chem. 2014;289:14881–95.PubMedCrossRef

60.

Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–89.PubMedCentralPubMedCrossRef

61.

Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F, Venturini E, Gregory L, Lonie L, Chew A, Wei CL, et al. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity. 2010;32:317–28.PubMedCrossRef

62.

Natoli G, Ghisletti S, Barozzi I. The genomic landscapes of inflammation. Genes Dev. 2011;25:101–6.PubMedCentralPubMedCrossRef

63.

Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H, Merad M, Jung S, Amit I. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. 2014;159:1312–26.PubMedCrossRef

64.

Gosselin D, Link VM, Romanoski CE, Fonseca GJ, Eichenfield DZ, Spann NJ, Stender JD, Chun HB, Garner H, Geissmann F, et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell. 2014;159:1327–40.PubMedCrossRef

65.

Gosselin D, Glass CK. Epigenomics of macrophages. Immunol Rev. 2014;262:96–112.PubMedCrossRef

66.

Egawa T, Tillman RE, Naoe Y, Taniuchi I, Littman DR. The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med. 2007;204:1945–57.PubMedCentralPubMedCrossRef

67.

Hollenhorst PC, Chandler KJ, Poulsen RL, Johnson WE, Speck NA, Graves BJ. DNA specificity determinants associate with distinct transcription factor functions. PLoS Genet. 2009;5:e1000778.PubMedCentralPubMedCrossRef

68.

Lepoivre C, Belhocine M, Bergon A, Griffon A, Yammine M, Vanhille L, Zacarias-Cabeza J, Garibal MA, Koch F, Maqbool MA, et al. Divergent transcription is associated with promoters of transcriptional regulators. BMC Genom. 2013;14:914.CrossRef

69.

Sun W, Graves BJ, Speck NA. Transactivation of the Moloney murine leukemia virus and T-cell receptor beta-chain enhancers by cbf and ets requires intact binding sites for both proteins. J Virol. 1995;69:4941–9.PubMedCentralPubMed

70.

Wotton D, Ghysdael J, Wang S, Speck NA, Owen MJ. Cooperative binding of Ets-1 and core binding factor to DNA. Mol Cell Biol. 1994;14:840–50.PubMedCentralPubMed

71.

Hayashi K, Natsume W, Watanabe T, Abe N, Iwai N, Okada H, Ito Y, Asano M, Iwakura Y, Habu S, et al. Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells. J Immunol. 2000;165:6816–24.PubMedCrossRef

72.

Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC, Komori T, Ito Y, Littman DR. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell. 2002;111:621–33.PubMedCrossRef

73.

Woolf E, Xiao C, Fainaru O, Lotem J, Rosen D, Negreanu V, Bernstein Y, Goldenberg D, Brenner O, Berke G, et al. Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis. Proc Natl Acad Sci USA. 2003;100:7731–6.PubMedCentralPubMedCrossRef

74.

Durst KL, Hiebert SW. Role of RUNX family members in transcriptional repression and gene silencing. Oncogene. 2004;23:4220–4.PubMedCrossRef

75.

Kohu K, Sato T, Ohno S, Hayashi K, Uchino R, Abe N, Nakazato M, Yoshida N, Kikuchi T, Iwakura Y, et al. Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage. J Immunol. 2005;174:2627–36.PubMedCrossRef

76.

Carpenter AC, Bosselut R. Decision checkpoints in the thymus. Nat Immunol. 2010;11:666–73.PubMedCentralPubMedCrossRef

77.

Komine O, Hayashi K, Natsume W, Watanabe T, Seki Y, Seki N, Yagi R, Sukzuki W, Tamauchi H, Hozumi K, et al. The Runx1 transcription factor inhibits the differentiation of naive CD4⁺ T cells into the Th2 lineage by repressing GATA3 expression. J Exp Med. 2003;198:51–61.PubMedCentralPubMedCrossRef

78.

Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M, Hatam F, Littman DR, Taniuchi I. Repression of interleukin-4 in T helper type 1 cells by RUNX/CBF beta binding to the Il4 silencer. J Exp Med. 2007;204:1749–55.PubMedCentralPubMedCrossRef

79.

Wong WF, Kohu K, Chiba T, Sato T, Satake M. Interplay of transcription factors in T-cell differentiation and function: the role of Runx. Immunology. 2011;132:157–64.PubMedCentralPubMedCrossRef

80.

Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T, Sakaguchi S. FOXP3 controls regulatory T-cell function by interacting with AML1/RUNX1. Nature. 2007;446:685–9.PubMedCrossRef

81.

Kitoh A, Ono M, Naoe Y, Ohkura N, Yamaguchi T, Yaguchi H, Kitabayashi I, Tsukada T, Nomura T, Miyachi Y, et al. Indispensable role of the RUNX1-CBFbeta transcription complex for in vivo-suppressive function of FOXP3+ regulatory T cells. Immunity. 2009;31:609–20.PubMedCrossRef

82.

Niebuhr B, Kriebitzsch N, Fischer M, Behrens K, Gunther T, Alawi M, Bergholz U, Muller U, Roscher S, Ziegler M, et al. Runx1 is essential at two stages of early murine B-cell development. Blood. 2013;122:413–23.PubMedCrossRef

83.

Seo W, Ikawa T, Kawamoto H, Taniuchi I. RUNX1-CBFbeta facilitates early B lymphocyte development by regulating expression of EBF1. J Exp Med. 2012;209:1255–62.PubMedCentralPubMedCrossRef

84.

Anderson MK, Weiss AH, Hernandez-Hoyos G, Dionne CJ, Rothenberg EV. Constitutive expression of PU.1 in fetal hematopoietic progenitors blocks T cell development at the pro-T cell stage. Immunity. 2002;16:285–96.PubMedCrossRef

85.

Dionne CJ, Tse KY, Weiss AH, Franco CB, Wiest DL, Anderson MK, Rothenberg EV. Subversion of T lineage commitment by PU.1 in a clonal cell line system. Dev Biol. 2005;280:448–66.PubMedCrossRef

86.

Del Real MM, Rothenberg EV. Architecture of a lymphomyeloid developmental switch controlled by PU.1, Notch and GATA3. Development. 2013;140:1207–19.PubMedCentralPubMedCrossRef

87.

Zhang JA, Mortazavi A, Williams BA, Wold BJ, Rothenberg EV. Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity. Cell. 2012;149:467–82.PubMedCentralPubMedCrossRef

88.

DeKoter RP, Singh H. Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science. 2000;288:1439–41.PubMedCrossRef

89.

Leddin M, Perrod C, Hoogenkamp M, Ghani S, Assi S, Heinz S, Wilson NK, Follows G, Schonheit J, Vockentanz L, et al. Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells. Blood. 2011;117:2827–38.PubMedCentralPubMedCrossRef

90.

Medina KL, Pongubala JM, Reddy KL, Lancki DW, Dekoter R, Kieslinger M, Grosschedl R, Singh H. Assembling a gene regulatory network for specification of the B cell fate. Dev Cell. 2004;7:607–17.PubMedCrossRef

91.

Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004;350:1535–48.PubMedCrossRef

92.

Della Gatta G, Palomero T, Perez-Garcia A, Ambesi-Impiombato A, Bansal M, Carpenter ZW, De Keersmaecker K, Sole X, Xu L, Paietta E, et al. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL. Nat Med. 2012;18:436–40.PubMedCrossRef

93.

Nasr MR, Rosenthal N, Syrbu S. Expression profiling of transcription factors in B- or T-acute lymphoblastic leukemia/lymphoma and burkitt lymphoma: usefulness of PAX5 immunostaining as pan-Pre-B-cell marker. Am J Clin Pathol. 2010;133:41–8.PubMedCrossRef

94.

Sokalski KM, Li SK, Welch I, Cadieux-Pitre HA, Gruca MR, DeKoter RP. Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia. Blood. 2011;118:2801–8.PubMedCrossRef

95.

McCune RC, Syrbu SI, Vasef MA. Expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB.1, and PU.1 in Hodgkin’s and non-Hodgkin’s lymphomas: a comparative study using high throughput tissue microarrays. Mod Pathol. 2006;19:1010–8.PubMedCrossRef

96.

Nottingham WT, Jarratt A, Burgess M, Speck CL, Cheng JF, Prabhakar S, Rubin EM, Li PS, Sloane-Stanley J, Kong ASJ, et al. Runx1-mediated hematopoietic stem-cell emergence is controlled by a GATA/ETS/SCL-regulated enhancer. Blood. 2007;110:4188–97.PubMedCentralPubMedCrossRef

97.

Chen H, Ray-Gallet D, Zhang P, Hetherington CJ, Gonzalez DA, Zhang DE, Moreau-Gachelin F, Tenen DG. PU.1 (Spi-1) autoregulates its expression in myeloid cells. Oncogene. 1995;11:1549–60.PubMed

98.

Ebralidze AK, Guibal FC, Steidl U, Zhang P, Lee S, Bartholdy B, Jorda MA, Petkova V, Rosenbauer F, Huang G, et al. PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. Genes Dev. 2008;22:2085–92.PubMedCentralPubMedCrossRef

99.

Hoogenkamp M, Lichtinger M, Krysinska H, Lancrin C, Clarke D, Williamson A, Mazzarella L, Ingram R, Jorgensen H, Fisher A, et al. Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program. Blood. 2009;114:299–309.PubMedCentralPubMedCrossRef

100.

Staber PB, Zhang P, Ye M, Welner RS, Levantini E, Di Ruscio A, Ebralidze AK, Bach C, Zhang H, Zhang J, et al. The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells. Blood. 2014;124:2391–9.PubMedCrossRef

101.

Rosenbauer F, Wagner K, Kutok JL, Iwasaki H, Le Beau MM, Okuno Y, Akashi K, Fiering S, Tenen DG. Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat Genet. 2004;36:624–30.PubMedCrossRef

102.

Huang G, Zhao X, Wang L, Elf S, Xu H, Sashida G, Zhang Y, Liu Y, Lee J, Menendez S, et al. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood. 2011;118:6544–52.PubMedCentralPubMedCrossRef

103.

Okada H, Watanabe T, Niki M, Takano H, Chiba N, Yanai N, Tani K, Hibino H, Asano S, Mucenski ML, et al. AML1(−/−) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene. Oncogene. 1998;17:2287–93.PubMedCrossRef

104.

Rosenbauer F, Owens BM, Yu L, Tumang JR, Steidl U, Kutok JL, Clayton LK, Wagner K, Scheller M, Iwasaki H, et al. Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Nat Genet. 2006;38:27–37.PubMedCrossRef

105.

Pozner A, Lotem J, Xiao C, Goldenberg D, Brenner O, Negreanu V, Levanon D, Groner Y. Developmentally regulated promoter-switch transcriptionally controls Runx1 function during embryonic hematopoiesis. BMC Dev Biol. 2007;7:84.PubMedCentralPubMedCrossRef

106.

Sroczynska P, Lancrin C, Kouskoff V, Lacaud G. The differential activities of RUNX1 promoters define milestones during embryonic hematopoiesis. Blood. 2009;114:5279–89.PubMedCrossRef

107.

Wong WF, Kurokawa M, Satake M, Kohu K. Down-regulation of RUNX1 expression by TCR signal involves an autoregulatory mechanism and contributes to IL-2 production. J Biol Chem. 2011;286:11110–8.PubMedCentralPubMedCrossRef

108.

Wong WF, Looi CY, Kon S, Movahed E, Funaki T, Chang LY, Satake M, Kohu K. T-cell receptor signaling induces proximal RUNX1 transactivation via a calcineurin-NFAT pathway. Eur J Immunol. 2014;44:894–904.PubMedCrossRef

109.

Bee T, Ashley EL, Bickley SR, Jarratt A, Li PS, Sloane-Stanley J, Gottgens B, de Bruijn MF. The mouse RUNX1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both RUNX1 promoters. Blood. 2009;113:5121–4.PubMedCrossRef

110.

Landry JR, Kinston S, Knezevic K, de Bruijn MF, Wilson N, Nottingham WT, Peitz M, Edenhofer F, Pimanda JE, Ottersbach K, et al. Runx genes are direct targets of SCL/TAL1 in the yolk sac and fetal liver. Blood. 2008;111:3005–14.PubMedCrossRef

111.

Zhao X, Chen A, Yan X, Zhang Y, He F, Hayashi Y, Dong Y, Rao Y, Li B, Conway RM, et al. Downregulation of RUNX1/CBFbeta by MLL fusion proteins enhances hematopoietic stem cell self-renewal. Blood. 2014;123:1729–38.PubMedCentralPubMedCrossRef

112.

Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J, Alpermann T, Haferlach C, Haferlach T. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood. 2011;117:2348–57.PubMedCrossRef

113.

Mangan JK, Speck NA. RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40 years in the making. Crit Rev Oncog. 2011;16:77–91.PubMedCentralPubMedCrossRef

114.

Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Rock J, Paschka P, Corbacioglu A, Krauter J, Schlegelberger B, Ganser A, et al. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol. 2011;29:1364–72.PubMedCrossRef

115.

Silva FP, Morolli B, Storlazzi CT, Anelli L, Wessels H, Bezrookove V, Kluin-Nelemans HC, Giphart-Gassler M. Identification of RUNX1/AML1 as a classical tumor suppressor gene. Oncogene. 2003;22:538–47.PubMedCrossRef

116.

Osato M, Asou N, Abdalla E, Hoshino K, Yamasaki H, Okubo T, Suzushima H, Takatsuki K, Kanno T, Shigesada K, et al. Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias. Blood. 1999;93:1817–24.PubMed

117.

Matheny CJ, Speck ME, Cushing PR, Zhou Y, Corpora T, Regan M, Newman M, Roudaia L, Speck CL, Gu TL, et al. Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. EMBO J. 2007;26:1163–75.PubMedCentralPubMedCrossRef

118.

Matsuno N, Osato M, Yamashita N, Yanagida M, Nanri T, Fukushima T, Motoji T, Kusumoto S, Towatari M, Suzuki R, et al. Dual mutations in the AML1 and FLT3 genes are associated with leukemogenesis in acute myeloblastic leukemia of the M0 subtype. Leukemia. 2003;17:2492–9.PubMedCrossRef

119.

Lam K, Zhang DE. RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis. Front Biosci (Landmark Ed). 2012;17:1120–39.CrossRef

120.

Nisson PE, Watkins PC, Sacchi N. Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t[8, 21] leukemic cells. Cancer Genet Cytogenet. 1992;63:81–8.PubMedCrossRef

121.

Meyers S, Lenny N, Hiebert SW. The t[8, 21] fusion protein interferes with AML-1B-dependent transcriptional activation. Mol Cell Biol. 1995;15:1974–82.PubMedCentralPubMed

122.

Ptasinska A, Assi SA, Mannari D, James SR, Williamson D, Dunne J, Hoogenkamp M, Wu M, Care M, McNeill H, et al. Depletion of RUNX1/ETO in t[8, 21] AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia. 2012;26:1829–41.PubMedCentralPubMedCrossRef

123.

Ptasinska A, Assi SA, Martinez-Soria N, Imperato MR, Piper J, Cauchy P, Pickin A, James SR, Hoogenkamp M, Williamson D, et al. Identification of a dynamic core transcriptional network in t[8, 21] AML that regulates differentiation block and self-renewal. Cell Rep. 2014;8:1974–88.PubMedCrossRef

124.

Sun XJ, Wang Z, Wang L, Jiang Y, Kost N, Soong TD, Chen WY, Tang Z, Nakadai T, Elemento O, et al. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature. 2013;500:93–7.PubMedCentralPubMedCrossRef

125.

Martens JH, Mandoli A, Simmer F, Wierenga BJ, Saeed S, Singh AA, Altucci L, Vellenga E, Stunnenberg HG. ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia. Blood. 2012;120:4038–48.PubMedCentralPubMedCrossRef

126.

Mandoli A, Singh AA, Jansen PW, Wierenga AT, Riahi H, Franci G, Prange K, Saeed S, Vellenga E, Vermeulen M, et al. CBFB-MYH11/RUNX1 together with a compendium of hematopoietic regulators, chromatin modifiers and basal transcription factors occupies self-renewal genes in inv[16] acute myeloid leukemia. Leukemia. 2014;28:770–8.PubMedCrossRef

127.

Ben-Ami O, Friedman D, Leshkowitz D, Goldenberg D, Orlovsky K, Pencovich N, Lotem J, Tanay A, Groner Y. Addiction of t[8, 21] and inv[16] acute myeloid leukemia to native RUNX1. Cell Rep. 2013;4:1131–43.PubMedCrossRef

128.

Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, Nakagawa M, Olsson A, Wunderlich M, Link KA, et al. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. J Clin Investig. 2013;123:3876–88.PubMedCentralPubMedCrossRef

129.

Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang DE, Tenen DG. AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t[8, 21] myeloid leukemia. Nat Med. 2001;7:444–51.PubMedCrossRef

130.

Mueller BU, Pabst T, Osato M, Asou N, Johansen LM, Minden MD, Behre G, Hiddemann W, Ito Y, Tenen DG. Heterozygous PU.1 mutations are associated with acute myeloid leukemia. Blood. 2002;100:998–1007.PubMedCrossRef

131.

The Cancer Genome Atlas Consortium. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368:2059–74.CrossRef

132.

Zhou J, Wu J, Li B, Liu D, Yu J, Yan X, Zheng S, Wang J, Zhang L, He F, et al. PU.1 is essential for MLL leukemia partially via crosstalk with the MEIS/HOX pathway. Leukemia. 2014;28:1436–48.PubMedCrossRef

133.

Steidl U, Steidl C, Ebralidze A, Chapuy B, Han HJ, Will B, Rosenbauer F, Becker A, Wagner K, Koschmieder S, et al. A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia. J Clin Invest. 2007;117:2611–20.PubMedCentralPubMedCrossRef

134.

Bonadies N, Pabst T, Mueller BU. Heterozygous deletion of the PU.1 locus in human AML. Blood. 2010;115:331–4.PubMedCrossRef

Titel: The RUNX1–PU.1 axis in the control of hematopoiesis
verfasst von: Maria Rosaria Imperato
Pierre Cauchy
Nadine Obier
Constanze Bonifer
Publikationsdatum: 01.04.2015
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 4/2015
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-015-1762-8

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

The RUNX1–PU.1 axis in the control of hematopoiesis

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2015

Guest editorial: Transcriptional control in myeloid cell development and related diseases

Successful pregnancy and delivery via in vitro fertilization with cryopreserved and thawed embryo transfer in an acute myeloid leukemia patient after allogeneic bone marrow transplantation

A randomized controlled study evaluating the efficacy of aprepitant for highly/moderately emetogenic chemotherapies in hematological malignancies

Regulation of myelopoiesis by the transcription factor IRF8

Third allogeneic stem cell transplantation (SCT) using unrelated cord blood for relapsed acute leukemia after second allogeneic SCT

Massive splenic hamartoma with bizarre stromal cells

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie