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Role of Polycomb-group genes in sustaining activities of normal and malignant stem cells

  • Progress in Hematology
  • Chromatin regulation in leukemogenesis
  • Published:
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Abstract

Polycomb-group genes (PcG), identified by Drosophila genetics, are believed to maintain positional information by constituting a cellular memory system. Recently this system has been proved to be supported by epigenetic transcription regulation. PcG products comprise two distinct complexes, PcG complex 1 and 2. First PcG complex 2 silences chromatin and encodes a histone code by methylating histone H3 at lysine 27. PcG complex 1 is, then, recruited by recognizing the histone code, and ubiquitinates histone H2A and/or inhibits chromatin remodeling to maintain the silenced states of the locus. Biologically, PcG-deficient mice provided biological evidence that PcG are essential for sustaining stem cell activity. More recently PcG were reported to be correlated with cancer progression and prognosis as well as with cancer stem cell activity. PcG may thus play a crucial part in sustaining the activities of malignant as well as normal stem cells. Although PcG were initially seen to maintain stem cell activity through repression of the INK4a locus, they now appear to perform more diverse functions in supporting stem cells. This paper summarizes current information on the molecular roles of PcG in normal and malignant stem cells and discusses the implications in future cancer therapy and regenerative medicine.

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References

  1. Griffin JD, Lowenberg B. Clonogenic cells in acute myeloblastic leukemia. Blood. 1986;68:1185–95.

    PubMed  CAS  Google Scholar 

  2. Kamel-Reid S, Dick JE. Engraftment of immune-deficient mice with human hematopoietic stem cells. Science. 1988;242:1706–9.

    Article  PubMed  CAS  Google Scholar 

  3. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–84.

    Article  PubMed  CAS  Google Scholar 

  4. Keith B, Simon MC. Hypoxia-inducible factors, stem cells, and cancer. Cell. 2007;129:465–72.

    Article  PubMed  CAS  Google Scholar 

  5. Piccirillo SGM, Reynolds BA, Zanetti N, et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006;444:761–5.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang J, Grindley JC, Yin T, et al. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature. 2006;441:518–22.

    Article  PubMed  CAS  Google Scholar 

  7. Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441:475–82.

    Article  PubMed  CAS  Google Scholar 

  8. Takihara Y, Hara J. Polycomb-group genes and hematopoiesis. Int J Hematol. 2000;72:165–72.

    PubMed  CAS  Google Scholar 

  9. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–5.

    Article  PubMed  CAS  Google Scholar 

  10. Ohta H, Sawada A, Kim J-Y, et al. Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells. J Exp Med. 2002;195:759–70.

    Article  PubMed  CAS  Google Scholar 

  11. Park IK, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302–5.

    Article  PubMed  CAS  Google Scholar 

  12. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003;425:962–7.

    Article  PubMed  CAS  Google Scholar 

  13. Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003;423:255–60.

    Article  PubMed  CAS  Google Scholar 

  14. Simon J. Locking in stable states of gene expression: transcriptional control during Drosophila development. Curr Opin Cell Biol. 1995;7:376–85.

    Article  PubMed  CAS  Google Scholar 

  15. Tkachuk DC, Kohler S, Cleary ML. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992;71:691–700.

    Article  PubMed  CAS  Google Scholar 

  16. Gu Y, Nakamura T, Alder H, et al. The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell. 1992;71:701–8.

    Article  PubMed  CAS  Google Scholar 

  17. Djabali M, Selleri L, Parry P, Bower M, Young BD, Evans GA. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet. 1992;2:113–8.

    Article  PubMed  CAS  Google Scholar 

  18. van der Lugt NMT, Domen J, Linders K, et al. Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 1994;8:757–69.

    Article  PubMed  Google Scholar 

  19. Akasaka T, Kanno M, Balling R, Mieza MA, Taniguchi M, Koseki H. A role for mel-18, a Polycomb group-related vertebrate gene, during the anteroposterior specification of the axial skeleton. Development. 1996;122:1513–22.

    PubMed  CAS  Google Scholar 

  20. Takihara Y, Tomotsune D, Shirai M, et al. Targeted disruption of the mouse homologue of the Drosophila polyhomeotic gene leads to altered anteroposterior patterning and neural crest defects. Development. 1997;124:3673–82.

    PubMed  CAS  Google Scholar 

  21. Core N, Bel S, Gaunt SJ, et al. Altered cellular proliferation and mesoderm patterning in polycomb-M33-deficient mice. Development. 1997;124:721–9.

    PubMed  CAS  Google Scholar 

  22. Katoh Fukui Y, Tsuchiya R, Shiroishi T, et al. Male-to-female sex reversal in M33 mutant mice. Nature. 1998;393:688–92.

    Article  PubMed  CAS  Google Scholar 

  23. Nowak K, Kerl K, Fehr D, et al. BMI1 is a target gene of E2F-1 and is strongly expressed in primary neuroblastomas. Nucleic Acids Res. 2006;34:1745–54.

    Article  PubMed  CAS  Google Scholar 

  24. Yang J, Chai L, Liu F, et al. Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci USA. 2007;104:10494–9.

    Article  PubMed  CAS  Google Scholar 

  25. Guo WJ, Zeng MS, Yadav A, et al. Mel-18 acts as a tumor suppressor by repressing Bmi-1 expression and down-regulating Akt activity in breast cancer cells. Cancer Res. 2007;67:5083–9.

    Article  PubMed  CAS  Google Scholar 

  26. Tomotsune D, Takihara Y, Berger J, et al. A novel member of murine polycomb-group proteins, sex comb on midleg homolog protein, is highly conserved, and interacts with RAE28/mph1 in vitro. Differentiation. 1999;65:229–39.

    Article  PubMed  CAS  Google Scholar 

  27. Lessard J, Baban S, Sauvageau G. Stage-specific expression of polycomb group genes in human bone marrow cells. Blood. 1998;91:1216–24.

    PubMed  CAS  Google Scholar 

  28. Lessard J, Sauvageau G. Polycomb group genes as epigenetic regulators of normal and leukemic hematopoiesis. Exp Hematol. 2003;31:567–85.

    Article  PubMed  CAS  Google Scholar 

  29. Takihara Y. Role of polycomb-group genes. Cell Technol. 2004;23:74–80.

    CAS  Google Scholar 

  30. van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet. 1999;23:474–8.

    Article  PubMed  Google Scholar 

  31. Vire E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439:871–4.

    Article  PubMed  CAS  Google Scholar 

  32. Cao R, Wang L, Wang H, et al. Role of hisotne H3 lysine 27 methylation in polycomb-group silencing. Science. 2002;298:1039–43.

    Article  PubMed  CAS  Google Scholar 

  33. Czermin B, Melfi R, McCabe D, Seitz V, Imhof A, Pirrotta V. Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransfease activity that marks chromosomal polycomb sites. Cell. 2002;111:185–96.

    Article  PubMed  CAS  Google Scholar 

  34. Muller J, Hart CM, Francis NJ, et al. Histone methyltransferase activity of a Drosophila polycomb group repressor complex. Cell. 2002;111:197–208.

    Article  PubMed  CAS  Google Scholar 

  35. Min J, Zhang Y, Xu RM. Structural basis for specific binding of polycomb chromodomain to histone H3 methylated at Lys 27. Genes Dev. 2003;17:1823–8.

    Article  PubMed  CAS  Google Scholar 

  36. Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by polycomb and HP1 chromodomains. Genes Dev. 2003;17:1870–81.

    Article  PubMed  CAS  Google Scholar 

  37. Shao Z, Raible F, Mollaaghababa R, et al. Stabilization of chromatin structure by PRC1, a polycomb complex. Cell. 1999;98:37–46.

    Article  PubMed  CAS  Google Scholar 

  38. Cao R, Tsukada Y, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell. 2005;20:845–54.

    Article  PubMed  CAS  Google Scholar 

  39. Mikkelsen TS, Ku M, Jaffe DB, et al. Genome-wide maps of chormatin state in pluripotent and lineage-committed cells. Nature. 2007;448:553–60.

    Article  PubMed  CAS  Google Scholar 

  40. Liu Y, Taverna SD, Muratore TL, Shabanowitz J, Hunt DF, Allis CD. RNAi-dependent H3K27 methylation is required for heterochromatin formation and DNA elimination in Tetrahymena. Genes Dev. 2007;21:1530–45.

    Article  PubMed  CAS  Google Scholar 

  41. Tomotsune D, Shirai M, Takihara Y, Shimada K. Regulation of Hoxb3 expression in the hindbrain and pharyngeal arches by rae28, a member of the mammalian polycomb group of genes. Mech Dev. 2000;98:165–9.

    Article  PubMed  CAS  Google Scholar 

  42. Bello B, Holbro N, Reichert H. Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila. Development. 2007;134:1091–9.

    Article  PubMed  CAS  Google Scholar 

  43. Kim JY, Sawada A, Tokimasa S, et al. Defective long-term repopulating ability in hematopoietic stem cells lacking the polycomb-group gene rae28. Eur J Haematol. 2004;73:75–84.

    Article  PubMed  CAS  Google Scholar 

  44. Iwama A, Oguro H, Negishi M, et al. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity. 2004;21:843–51.

    Article  PubMed  CAS  Google Scholar 

  45. Kajiume T, Ninomiya Y, Ishihara H, Kanno R, Kanno M. Polycomb group gene mel-18 modulates the self-renewal activity and cell cycle status of hematopoietic stem cells. Exp Hematol. 2004;32:571–8.

    Article  PubMed  CAS  Google Scholar 

  46. Leung C, Lingbeek M, Shakhova O et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature. 2004;428:337–41.

    Article  PubMed  CAS  Google Scholar 

  47. O’Carroll D, Erhardt S, Pagani M, Barton SC, Surani MA, Jenuwein T. The polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol. 2001;21:4330–6.

    Article  PubMed  CAS  Google Scholar 

  48. Lessard J, Schumacher A, Thorsteinsdottir U, van Lohuizen M, Magnuson T, Sauvageau G. Functional antagonism of the polycomb-group genes eed and Bmi1 in hemopoietic cell proliferation. Genes Dev. 1999;13:2691–703.

    Article  PubMed  CAS  Google Scholar 

  49. Kamminga LM, Bystrykh LV, de Boer A, et al. The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood. 2006;107:2170–9.

    Article  PubMed  CAS  Google Scholar 

  50. Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 2005;19:1432–7.

    Article  PubMed  CAS  Google Scholar 

  51. Oguro H, Iwama A, Morita Y, Kamijo T, van Lohuizen M, Nakauchi H. Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient mice. J Exp Med. 2006;203:2247–53.

    Article  PubMed  CAS  Google Scholar 

  52. Bruggeman SWM, Valk-Lingbeek ME, van der Stoop PPM, et al. Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. Genes Dev. 2005;19:1438–43.

    Article  PubMed  CAS  Google Scholar 

  53. Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y. pRB family proteins are required for H3K27 trimethylaion and polycomb repression complexes binding to and silencing p16INK4a tumor suppressor gene. Genes Dev. 2007;21:49–54.

    Article  PubMed  CAS  Google Scholar 

  54. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, et al. The polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 2007;21:525–30.

    Article  PubMed  CAS  Google Scholar 

  55. Jacobs JJ, Kieboom K, Marino S, DePinho RA, van Lohuizen M. The oncogene and polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature. 1999;397:164–8.

    Article  PubMed  CAS  Google Scholar 

  56. Gil J, Bernard D, Martinez D, Beach D. Polycomb CBX7 has a unifying role in cellular lifespan. Nat Cell Biol. 2004;6:67–72.

    Article  PubMed  CAS  Google Scholar 

  57. Dietrich N, Bracken AP, Trinh E, et al. Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus. EMBO J. 2007;26:1637–48.

    Article  PubMed  CAS  Google Scholar 

  58. Stepanova L, Sorrentino BP. A limited role for p16Ink4a and p19Arf in the loss of hematopoietic stem cells during proliferative stress. Blood. 2005;106:827–32.

    Article  PubMed  CAS  Google Scholar 

  59. Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y. A complex with chromatin modifires that occupies E2F- and Myc-responsive gene in G0 cells. Science. 2002;296:1132–6.

    Article  PubMed  CAS  Google Scholar 

  60. Trimarchi JM, Fairchild B, Wen J, Lees JA. The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex. Proc Natl Acad Sci USA. 2001;98:1519–24.

    Article  PubMed  CAS  Google Scholar 

  61. Aslanian A, Iaquinta PJ, Verona R, Lees JA. Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics. Genes Dev. 2004;18:1413–22.

    Article  PubMed  CAS  Google Scholar 

  62. Dahiya A, Wong S, Gonzalo S, Gavin M, Dean DC. Linking the Rb and polycomb pathways. Mol Cell. 2001;8:557–69.

    Article  PubMed  CAS  Google Scholar 

  63. Goodliffe JM, Wieschaus E, Cole MD. Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila. Genes Dev. 2005;19:2941–6.

    Article  PubMed  CAS  Google Scholar 

  64. Ferres-Marco D, Gutierrez-Garcia I, Vallejo DM, Bolivar J, Gutierrez-Avino FJ, Dominguez M. Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing. Nature. 2006;439:430–6.

    Article  PubMed  CAS  Google Scholar 

  65. Chagraoui J, Niessen SL, Lessard J, et al. E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 2006;20:2110–20.

    Article  PubMed  CAS  Google Scholar 

  66. Le Cam L, Linares LK, Paul C, et al. E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation. Cell. 2006;127:775–88.

    Article  PubMed  CAS  Google Scholar 

  67. Fernandes ER, Zhang JY, Rooney RJ. Adenovirus E1A-regulated transcription factor p120E4F inhibits cell growth and induces the stabilization of the cdk inhibitor p21WAF1. Mol Cell Biol. 1998;18:459–67.

    PubMed  CAS  Google Scholar 

  68. Luo L, Yang X, Takihara Y, Knoetgen H, Kessel M. The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions. Nature. 2004;427:749–53.

    Article  PubMed  CAS  Google Scholar 

  69. Madine M, Laskey R. Geminin bans replication licence. Nat Cell Biol. 2001;3:E49–50.

    Article  PubMed  CAS  Google Scholar 

  70. Seo S, Herr A, Lim JW, Richardson GA, Richardson H, Kroll KL. Geminin regulates neuronal differentiation by antagonizing Brg1 activity. Genes Dev. 2005;19:1732–4.

    Article  Google Scholar 

  71. Lee TI, Jenner RG, Boyer LA, et al. Control of developmental regulators by polycomb in human embryonic stem cells. Cell. 2006;125:301–13.

    Article  PubMed  CAS  Google Scholar 

  72. Boyer LA, Plath K, Zeitlinger J, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature. 2006;441:349–53.

    Article  PubMed  CAS  Google Scholar 

  73. van Lohuizen M, Verbeek S, Scheijen B, Wientjens E, van der Gulden H, Berns A. Identification of cooperating oncogenes in Emu-myc transgenic mice by provirus tagging. Cell. 1991;65:737–52.

    Article  PubMed  Google Scholar 

  74. Haupt Y, Alexander WS, Barri G, Klinken SP, Adams JM. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Emu-myc transgenic mice. Cell. 1991;65:753–63.

    Article  PubMed  CAS  Google Scholar 

  75. Jacobs JJL, Scheijen B, Voncken JW, Kieboom K, Berns A, van Lohuizen M. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev. 1999;13:2678–90.

    Article  PubMed  CAS  Google Scholar 

  76. Smith KS, Chanda SK, Lingbeek M, et al. Bmi-1 regulation of INK4A-ARF is a downstream requirement for transformation of hematopoietic progenitors by E2a-Pbx1. Mol Cell. 2003;12:393–400.

    Article  PubMed  CAS  Google Scholar 

  77. Villa R, Pasini D, Gutierrez A, et al. Role of the polycomb repressive complex 2 in acute promyelocytic leukemia. Cancer Cell. 2007;11:513–25.

    Article  PubMed  CAS  Google Scholar 

  78. Sawa M, Yamamoto K, Yokozawa T, et al. BMI-1 is highly expressed in M0-subtype acute myeloid leukemia. Int J Hematol. 2005;82:42–7.

    Article  PubMed  CAS  Google Scholar 

  79. Chowdhury M, Mihara K, Yasunaga S, Ohtaki M, Takihara Y, Kimura A. Expression of polycomb-group (PcG) protein BMI-1 predicts prognosis in patients with acute myeloid leukemia. Leukemia. 2007;21:1116–22.

    PubMed  CAS  Google Scholar 

  80. Mohty M, Yong SSM, Szydlo RM, Apperley JF, Melo JV. The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood. 2007;110:380–3.

    Article  PubMed  CAS  Google Scholar 

  81. Mihara K, Chowdury M, Nakaju N, et al. Bmi-1 is useful as a novel molecular maker for predicting progression of myelodysplatic syndrome and patient prognosis. Blood. 2006;107:305–8.

    Article  PubMed  CAS  Google Scholar 

  82. Bea S, Torf F, Pinyol M, et al. BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res. 2001;61:2409–12.

    PubMed  CAS  Google Scholar 

  83. Kim JH, Yoon SY, Kim CN, et al. The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlated with the reduced p16INK4a/p14ARF protein. Cancer Lett. 2004;203:217–24.

    Article  PubMed  CAS  Google Scholar 

  84. Neo SY, Leow CK, Vega VB, et al. Identification of discriminators of hepatoma by gene expression profiling using a minimal dataset approach. Hepatology. 2004;39:944–53.

    Article  PubMed  CAS  Google Scholar 

  85. Vonlanthen S, Heighway J, Altermatt HJ, et al. The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlated with INK4A-ARF locus expression. Br J Cancer. 2001;84:1372–6.

    Article  PubMed  CAS  Google Scholar 

  86. Dimri GP, Martinez JL, Jacobs JJ, et al. The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Res. 2002;62:4736–45.

    PubMed  CAS  Google Scholar 

  87. Kleer CG, Cao Q, Varambally S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA. 2003;100:11606–11.

    Article  PubMed  CAS  Google Scholar 

  88. Varambally S, Dhanasekaran SM, Zhou M, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419:624–9.

    Article  PubMed  CAS  Google Scholar 

  89. Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006;66:6063–71.

    Article  PubMed  CAS  Google Scholar 

  90. Stingl J, Eirew P, Ricketson I, et al. Purification and unique properties of mammary epithelial stem cells. Nature. 2006;439:993–7.

    PubMed  CAS  Google Scholar 

  91. Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving Imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.

    Article  PubMed  CAS  Google Scholar 

  92. Michor F, Hughes TP, Iwasa Y, et al. Dynamics of chronic myeloid leukaemia. Nature. 2005;435:1267–70.

    Article  PubMed  CAS  Google Scholar 

  93. Liu L, Amndrew LG, Tollefsbol T. Loss of the human polycomb group protein BMI1 promotes cancer-specific cell death. Oncogene. 2006;25:4370–5.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Uehara Memorial Foundation, Yamanouchi Foundation for Research on Metabolic Disorders, Japan Leukaemia Research Fund, Mitsubishi Pharma Research Foundation, Novartis Foundation for the Promotion of Science, and Daiwa Securities Health foundation. The author thanks Drs. M. Kobayashi, M. Ohtsubo, S. Yasunaga, K. Mihara, Y. Ohno and M. Tsumura for helpful discussion, and Leukemia Program Project of Hiroshima University for encouragement.

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  1. Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 2-3, Kasumi-1, Minami-ku, Hiroshima, 734-8553, Japan

    Yoshihiro Takihara

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Takihara, Y. Role of Polycomb-group genes in sustaining activities of normal and malignant stem cells. Int J Hematol 87, 25–34 (2008). https://doi.org/10.1007/s12185-007-0006-y

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