Skip to main content
SpringerLink
Log in

ENL: structure, function, and roles in hematopoiesis and acute myeloid leukemia

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

ENL/MLLT1 is a distinctive member of the KMT2 family based on its structural homology. ENL is a histone acetylation reader and a critical component of the super elongation complex. ENL plays pivotal roles in the regulation of chromatin remodelling and gene expression of many important proto-oncogenes, such as Myc, Hox genes, via histone acetylation. Novel insights of the key role of the YEATS domain of ENL in the transcriptional control of leukemogenic gene expression has emerged from whole genome Crisp-cas9 studies in acute myeloid leukemia (AML). In this review, we have summarized what is currently known about the structure and function of the ENL molecule. We described the ENL’s role in normal hematopoiesis, and leukemogenesis. We have also outlined the detailed molecular mechanisms underlying the regulation of target gene expression by ENL, as well as its major interacting partners and complexes involved. Finally, we discuss the emerging knowledge of different approaches for the validation of ENL as a therapeutic target and the development of small-molecule inhibitors disrupting the YEATS reader pocket of ENL protein, which holds great promise for the treatment of AML. This review will not only provide a fundamental understanding of the structure and function of ENL and update on the roles of ENL in AML, but also the development of new therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wei AH, Tiong IS (2017) Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Blood 130:2469–2474

    Article  CAS  PubMed  Google Scholar 

  2. Klepin HD, Rao AV, Pardee TS (2014) Acute myeloid leukemia and myelodysplastic syndromes in older adults. J Clin Oncol 32:2541–2552

    Article  PubMed Central  PubMed  Google Scholar 

  3. Zhou J, Chan ZL, Bi C, Lu X, Chong PS, Chooi JY, Cheong LL, Liu SC, Ching YQ, Zhou Y et al (2017) LIN28B activation by PRL-3 promotes leukemogenesis and a stem cell-like transcriptional program in AML. Mol Cancer Res 15:294–303

    Article  CAS  PubMed  Google Scholar 

  4. Sanz MA, Iacoboni G, Montesinos P, Venditti A (2016) Emerging strategies for the treatment of older patients with acute myeloid leukemia. Ann Hematol 95:1583–1593

    Article  PubMed  Google Scholar 

  5. Zhou J, Chng WJ (2014) Identification and targeting leukemia stem cells: the path to the cure for acute myeloid leukemia. World J Stem Cells 6:473–484

    Article  PubMed Central  PubMed  Google Scholar 

  6. Bret C, Viziteu E, Kassambara A, Moreaux J (2016) Identifying high-risk adult AML patients: epigenetic and genetic risk factors and their implications for therapy. Expert Rev Hematol 9:351–360

    Article  CAS  PubMed  Google Scholar 

  7. Ohgami RS, Arber DA (2015) The diagnostic and clinical impact of genetics and epigenetics in acute myeloid leukemia. Int J Lab Hematol 37(Suppl 1):122–132

    Article  PubMed  Google Scholar 

  8. Meyer C, Hofmann J, Burmeister T, Groger D, Park TS, Emerenciano M, Pombo de Oliveira M, Renneville A, Villarese P, Macintyre E et al (2013) The MLL recombinome of acute leukemias in 2013. Leukemia 27:2165–2176

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Sun QY, Ding LW, Tan KT, Chien W, Mayakonda A, Lin DC, Loh XY, Xiao JF, Meggendorfer M, Alpermann T et al (2017) Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD). Leukemia 31:1–10

    Article  CAS  PubMed  Google Scholar 

  10. Winters AC, Bernt KM (2017) MLL-rearranged leukemias-an update on science and clinical approaches. Front Pediatr 5:4

    Article  PubMed Central  PubMed  Google Scholar 

  11. Zeisig DT, Bittner CB, Zeisig BB, Garcia-Cuellar MP, Hess JL, Slany RK (2005) The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin. Oncogene 24:5525–5532

    Article  CAS  PubMed  Google Scholar 

  12. Muntean AG, Hess JL (2012) The pathogenesis of mixed-lineage leukemia. Annu Rev Pathol 7:283–301

    Article  CAS  PubMed  Google Scholar 

  13. Perlman EJ, Gadd S, Arold ST, Radhakrishnan A, Gerhard DS, Jennings L, Huff V, Guidry Auvil JM, Davidsen TM, Dome JS et al (2015) MLLT1 YEATS domain mutations in clinically distinctive favourable histology wilms tumours. Nat Commun 6:10013

    Article  CAS  PubMed  Google Scholar 

  14. Erb MA, Scott TG, Li BE, Xie H, Paulk J, Seo HS, Souza A, Roberts JM, Dastjerdi S, Buckley DL et al (2017) Transcription control by the ENL YEATS domain in acute leukaemia. Nature 543:270–274

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Wan L, Wen H, Li Y, Lyu J, Xi Y, Hoshii T, Joseph JK, Wang X, Loh YE, Erb MA et al (2017) ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia. Nature 543:265–269

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Garcia-Cuellar MP, Zilles O, Schreiner SA, Birke M, Winkler TH, Slany RK (2001) The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human Polycomb 3. Oncogene 20:411–419

    Article  CAS  PubMed  Google Scholar 

  17. Schulze JM, Wang AY, Kobor MS (2009) YEATS domain proteins: a diverse family with many links to chromatin modification and transcription. Biochem Cell Biol 87:65–75

    Article  CAS  PubMed  Google Scholar 

  18. Ui A, Yasui A (2016) Collaboration of MLLT1/ENL, polycomb and ATM for transcription and genome integrity. Nucleus 7:138–145

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Le Masson I, Yu DY, Jensen K, Chevalier A, Courbeyrette R, Boulard Y, Smith MM, Mann C (2003) Yaf9, a novel NuA4 histone acetyltransferase subunit, is required for the cellular response to spindle stress in yeast. Mol Cell Biol 23:6086–6102

    Article  PubMed Central  PubMed  Google Scholar 

  20. Wilkinson AW, Gozani O (2017) Cancer epigenetics: reading the future of leukaemia. Nature 543:186–188

    Article  CAS  PubMed  Google Scholar 

  21. Ayton PM, Cleary ML (2001) Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 20:5695–5707

    Article  CAS  PubMed  Google Scholar 

  22. Slany RK, Lavau C, Cleary ML (1998) The oncogenic capacity of HRX-ENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX. Mol Cell Biol 18:122–129

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Zhao D, Li Y, Xiong X, Chen Z, Li H (2017) YEATS domain-A histone acylation reader in health and disease. J Mol Biol 429:1994–2002

    Article  CAS  PubMed  Google Scholar 

  24. Okuda H, Stanojevic B, Kanai A, Kawamura T, Takahashi S, Matsui H, Takaori-Kondo A, Yokoyama A (2017) Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia. J Clin Invest 127:1918–1931

    Article  PubMed Central  PubMed  Google Scholar 

  25. Mueller D, Bach C, Zeisig D, Garcia-Cuellar MP, Monroe S, Sreekumar A, Zhou R, Nesvizhskii A, Chinnaiyan A, Hess JL, Slany RK (2007) A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 110:4445–4454

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Doty RT, Vanasse GJ, Disteche CM, Willerford DM (2002) The leukemia-associated gene Mllt1/ENL: characterization of a murine homolog and demonstration of an essential role in embryonic development. Blood Cells Mol Dis 28:407–417

    Article  PubMed  Google Scholar 

  27. Huret JL, Brizard A, Slater R, Charrin C, Bertheas MF, Guilhot F, Hahlen K, Kroes W, van Leeuwen E, Schoot EV et al (1993) Cytogenetic heterogeneity in t(11;19) acute leukemia: clinical, hematological and cytogenetic analyses of 48 patients–updated published cases and 16 new observations. Leukemia 7:152–160

    CAS  PubMed  Google Scholar 

  28. Zhou J, Bi C, Ching YQ, Chooi JY, Lu X, Quah JY, Toh SH, Chan ZL, Tan TZ, Chong PS, Chng WJ (2017) Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia. J Hematol Oncol 10:138

    Article  PubMed Central  PubMed  Google Scholar 

  29. Shih LY, Liang DC, Fu JF, Wu JH, Wang PN, Lin TL, Dunn P, Kuo MC, Tang TC, Lin TH, Lai CL (2006) Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement. Leukemia 20:218–223

    Article  CAS  PubMed  Google Scholar 

  30. Garcia-Cuellar MP, Schreiner SA, Birke M, Hamacher M, Fey GH, Slany RK (2000) ENL, the MLL fusion partner in t(11;19), binds to the c-Abl interactor protein 1 (ABI1) that is fused to MLL in t(10;11)+. Oncogene 19:1744–1751

    Article  CAS  PubMed  Google Scholar 

  31. Buechele C, Breese EH, Schneidawind D, Lin CH, Jeong J, Duque-Afonso J, Wong SH, Smith KS, Negrin RS, Porteus M, Cleary ML (2015) MLL leukemia induction by genome editing of human CD34 + hematopoietic cells. Blood 126:1683–1694

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Reimer J, Knoss S, Labuhn M, Charpentier EM, Gohring G, Schlegelberger B, Klusmann JH, Heckl D (2017) CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo. Haematologica 102:1558–1566

    Article  PubMed Central  PubMed  Google Scholar 

  33. Drynan LF, Pannell R, Forster A, Chan NM, Cano F, Daser A, Rabbitts TH (2005) Mll fusions generated by Cre-loxP-mediated de novo translocations can induce lineage reassignment in tumorigenesis. EMBO J 24:3136–3146

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Takacova S, Slany R, Bartkova J, Stranecky V, Dolezel P, Luzna P, Bartek J, Divoky V (2012) DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo. Cancer Cell 21:517–531

    Article  CAS  PubMed  Google Scholar 

  35. Ugale A, Sawen P, Dudenhoffer-Pfeifer M, Wahlestedt M, Norddahl GL, Bryder D (2017) MLL-ENL-mediated leukemia initiation at the interface of lymphoid commitment. Oncogene 36:3207–3212

    Article  CAS  PubMed  Google Scholar 

  36. Horton SJ, Walf-Vorderwulbecke V, Chatters SJ, Sebire NJ, de Boer J, Williams O (2009) Acute myeloid leukemia induced by MLL-ENL is cured by oncogene ablation despite acquisition of complex genetic abnormalities. Blood 113:4922–4929

    Article  CAS  PubMed  Google Scholar 

  37. Nakata J, Nakano K, Okumura A, Mizutani Y, Kinoshita H, Iwai M, Hasegawa K, Morimoto S, Fujiki F, Tatsumi N et al (2014) In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity. Leukemia 28:1316–1325

    Article  CAS  PubMed  Google Scholar 

  38. Cano F, Drynan LF, Pannell R, Rabbitts TH (2008) Leukaemia lineage specification caused by cell-specific Mll-Enl translocations. Oncogene 27:1945–1950

    Article  CAS  PubMed  Google Scholar 

  39. Zeisig BB, Milne T, Garcia-Cuellar MP, Schreiner S, Martin ME, Fuchs U, Borkhardt A, Chanda SK, Walker J, Soden R et al (2004) Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol 24:617–628

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Schreiner S, Birke M, Garcia-Cuellar MP, Zilles O, Greil J, Slany RK (2001) MLL-ENL causes a reversible and myc-dependent block of myelomonocytic cell differentiation. Cancer Res 61:6480–6486

    CAS  PubMed  Google Scholar 

  41. Arai S, Yoshimi A, Shimabe M, Ichikawa M, Nakagawa M, Imai Y, Goyama S, Kurokawa M (2011) Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells. Blood 117:6304–6314

    Article  CAS  PubMed  Google Scholar 

  42. Ayton PM, Cleary ML (2003) Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9. Genes Dev 17:2298–2307

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Faber J, Krivtsov AV, Stubbs MC, Wright R, Davis TN, van den Heuvel-Eibrink M, Zwaan CM, Kung AL, Armstrong SA (2009) HOXA9 is required for survival in human MLL-rearranged acute leukemias. Blood 113:2375–2385

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Horton SJ, Grier DG, McGonigle GJ, Thompson A, Morrow M, De Silva I, Moulding DA, Kioussis D, Lappin TR, Brady HJ, Williams O (2005) Continuous MLL-ENL expression is necessary to establish a “Hox Code” and maintain immortalization of hematopoietic progenitor cells. Cancer Res 65:9245–9252

    Article  CAS  PubMed  Google Scholar 

  45. Jin S, Zhao H, Yi Y, Nakata Y, Kalota A, Gewirtz AM (2010) c-Myb binds MLL through menin in human leukemia cells and is an important driver of MLL-associated leukemogenesis. J Clin Invest 120:593–606

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Milne TA, Martin ME, Brock HW, Slany RK, Hess JL (2005) Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9 locus, promoting transcription and multiple histone modifications. Cancer Res 65:11367–11374

    Article  CAS  PubMed  Google Scholar 

  47. Schwieger M, Schuler A, Forster M, Engelmann A, Arnold MA, Delwel R, Valk PJ, Lohler J, Slany RK, Olson EN, Stocking C (2009) Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C. Blood 114:2476–2488

    Article  CAS  PubMed  Google Scholar 

  48. Wang QF, Wu G, Mi S, He F, Wu J, Dong J, Luo RT, Mattison R, Kaberlein JJ, Prabhakar S et al (2011) MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome. Blood 117:6895–6905

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Armstrong SA, Kung AL, Mabon ME, Silverman LB, Stam RW, Den Boer ML, Pieters R, Kersey JH, Sallan SE, Fletcher JA et al (2003) Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell 3:173–183

    Article  CAS  PubMed  Google Scholar 

  50. Kazi JU, Chougule RA, Li T, Su X, Moharram SA, Rupar K, Marhall A, Gazi M, Sun J, Zhao H, Ronnstrand L (2017) Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD. Cell Mol Life Sci 74:2679–2688

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Zhou J, Goh BC, Albert DH, Chen CS (2009) ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside. J Hematol Oncol 2:33

    Article  PubMed Central  PubMed  Google Scholar 

  52. Walf-Vorderwulbecke V, de Boer J, Horton SJ, van Amerongen R, Proost N, Berns A, Williams O (2012) Frat2 mediates the oncogenic activation of Rac by MLL fusions. Blood 120:4819–4828

    Article  CAS  PubMed  Google Scholar 

  53. Schwartz YB, Pirrotta V (2013) A new world of Polycombs: unexpected partnerships and emerging functions. Nat Rev Genet 14:853–864

    Article  CAS  PubMed  Google Scholar 

  54. Takamatsu-Ichihara E, Kitabayashi I (2016) The roles of Polycomb group proteins in hematopoietic stem cells and hematological malignancies. Int J Hematol 103:634–642

    Article  CAS  PubMed  Google Scholar 

  55. Zhou J, Bi C, Cheong LL, Mahara S, Liu SC, Tay KG, Koh TL, Yu Q, Chng WJ (2011) The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML. Blood 118:2830–2839

    Article  PubMed  Google Scholar 

  56. Maethner E, Garcia-Cuellar MP, Breitinger C, Takacova S, Divoky V, Hess JL, Slany RK (2013) MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells. Cell Rep 3:1553–1566

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Ui A, Nagaura Y, Yasui A (2015) Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair. Mol Cell 58:468–482

    Article  CAS  PubMed  Google Scholar 

  58. Chen R, Yik JH, Lew QJ, Chao SH (2014) Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer. Biomed Res Int 2014:232870

    PubMed  PubMed Central  Google Scholar 

  59. Garcia-Cuellar MP, Buttner C, Bartenhagen C, Dugas M, Slany RK (2016) Leukemogenic MLL-ENL fusions induce alternative chromatin states to drive a functionally dichotomous group of target genes. Cell Rep 15:310–322

    Article  CAS  PubMed  Google Scholar 

  60. Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary ML (2010) A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell 17:198–212

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Wang X, Chen CW, Armstrong SA (2016) The role of DOT1L in the maintenance of leukemia gene expression. Curr Opin Genet Dev 36:68–72

    Article  PubMed  Google Scholar 

  62. van Leeuwen F, Gafken PR, Gottschling DE (2002) Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell 109:745–756

    Article  PubMed  Google Scholar 

  63. Mohan M, Herz HM, Takahashi YH, Lin C, Lai KC, Zhang Y, Washburn MP, Florens L, Shilatifard A (2010) Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes Dev 24:574–589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Nguyen AT, Taranova O, He J, Zhang Y (2011) DOT1L, the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis. Blood 117:6912–6922

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L et al (2011) MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 20:66–78

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Kuntimaddi A, Achille NJ, Thorpe J, Lokken AA, Singh R, Hemenway CS, Adli M, Zeleznik-Le NJ, Bushweller JH (2015) Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential. Cell Rep 11:808–820

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, Su L, Xu G, Zhang Y (2005) hDOT1L links histone methylation to leukemogenesis. Cell 121:167–178

    Article  CAS  PubMed  Google Scholar 

  68. Jaracz-Ros A, Lewandowski D, Barroca V, Lavau C, Romeo PH (2011) MLL-ENL leukemia burden initiated in femoral diaphysis and preceded by mature B-cell depletion. Haematologica 96:1770–1778

    Article  PubMed Central  PubMed  Google Scholar 

  69. Research Watch (2017) ENL is an essential acetyl-histone reader in acute myeloid leukemia. Cancer Discov 7:OF14

    Google Scholar 

  70. Zhou J, Lu X, Tan TZ, Chng WJ (2018) X-linked inhibitor of apoptosis inhibition sensitizes acute myeloid leukemia cell response to TRAIL and chemotherapy through potentiated induction of proapoptotic machinery. Mol Oncol 12:33–47

    Article  CAS  PubMed  Google Scholar 

  71. Hu Y, Li S (2016) Survival regulation of leukemia stem cells. Cell Mol Life Sci 73:1039–1050

    Article  CAS  PubMed  Google Scholar 

  72. Huber R, Pietsch D, Gunther J, Welz B, Vogt N, Brand K (2014) Regulation of monocyte differentiation by specific signaling modules and associated transcription factor networks. Cell Mol Life Sci 71:63–92

    Article  CAS  PubMed  Google Scholar 

  73. Stein EM, Garcia-Manero G, Rizzieri DA, Tibes R, Berdeja JG, Savona MR, Jongen-Lavrenic M, Altman JK, Thomson B, Blakemore SJ et al (2018) The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia. Blood 131:2661–2669

    Article  PubMed Central  PubMed  Google Scholar 

  74. Boffo S, Damato A, Alfano L, Giordano A (2018) CDK9 inhibitors in acute myeloid leukemia. J Exp Clin Cancer Res 37:36

    Article  PubMed Central  PubMed  Google Scholar 

  75. Gerlach D, Tontsch-Grunt U, Baum A, Popow J, Scharn D, Hofmann MH, Engelhardt H, Kaya O, Beck J, Schweifer N et al (2018) The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML. Oncogene 37:2687–2701

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Morales F, Giordano A (2016) Overview of CDK9 as a target in cancer research. Cell Cycle 15:519–527

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Lucking U, Scholz A, Lienau P, Siemeister G, Kosemund D, Bohlmann R, Briem H, Terebesi I, Meyer K, Prelle K et al (2017) Identification of Atuveciclib (BAY 1143572), the first highly selective, clinical PTEFb/CDK9 inhibitor for the treatment of cancer. ChemMedChem 12:1776–1793

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Ms Celestina Chin Ai Qi (CSI Singapore) for writing editing.

Funding

This research is supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative (WJ Chng) and NMRC Clinician-Scientist IRG Grant CNIG11nov38 (J.Z.). W.J.C. is also supported by NMRC Clinician Scientist Investigator award. This study is also partially supported by the RNA Biology Center at CSI Singapore, NUS, from funding by the Singapore Ministry of Education’s Tier 3 Grants, Grant number MOE2014-T3-1-006.

Author information

Authors and Affiliations

  1. Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599, Republic of Singapore

    Jianbiao Zhou, Yvonne Ng & Wee-Joo Chng

  2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Republic of Singapore

    Jianbiao Zhou & Wee-Joo Chng

  3. Department of Hematology-Oncology, National University Cancer Institute of Singapore (NCIS), The National University Health System (NUHS), 1E, Kent Ridge Road, Singapore, 119228, Republic of Singapore

    Wee-Joo Chng

Authors
  1. Jianbiao Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yvonne Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wee-Joo Chng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JZ, YN, and WJC summarized the literature and wrote the paper. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jianbiao Zhou or Wee-Joo Chng.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, J., Ng, Y. & Chng, WJ. ENL: structure, function, and roles in hematopoiesis and acute myeloid leukemia. Cell. Mol. Life Sci. 75, 3931–3941 (2018). https://doi.org/10.1007/s00018-018-2895-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-018-2895-8

Keywords

Search

Navigation