Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Transcriptional control and signal transduction, cell cycle

Determinants and role of chromatin organization in acute leukemia

Leukemia volume 34, pages 2561–2575 (2020)Cite this article

Subjects

Abstract

DNA is compacted into higher order structures that have major implications in gene regulation. These structures allow for long-range interactions of DNA elements, such as the association of promoters with their cognate enhancers. In recent years, mutations in genes that control these structures, including the cohesin-complex and the insulator-binding protein CTCF, have been found in a spectrum of hematologic disorders, and especially in acute leukemias. Cohesin and CTCF are critical for mediating looping and establishing boundaries within chromatin. Cells that harbor mutations in these genes display aberrant chromatin architecture and resulting differences in gene expression that contribute to leukemia initiation and progression. Here, we provide detailed discussion of the nature of 3D interactions and the way that they are disrupted in acute leukemia. Continued research in this area will provide new insights into the mechanisms of leukemogenesis and may shed light on novel treatment strategies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Working model for the role of CTCF and cohesion in chromatin looping.
Fig. 2: Models of looping alteration schemes observed in leukemias.
Fig. 3: The MYC locus as a model of chromatin looping and associated mechanisms in acute leukemia.

Similar content being viewed by others

References

  1. Lupiáñez DG, Spielmann M, Mundlos S. Breaking TADs: how alterations of chromatin domains result in disease. Trends Genet. 2016;32:225–37.

    Article  PubMed  CAS  Google Scholar 

  2. Dekker J, Mirny L. The 3D genome as moderator of chromosomal communication. Cell. 2016;164:1110–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Eagen KP. Principles of chromosome architecture revealed by Hi-C. Trends Biochemical Sci. 2018;43:469–78.

    Article  CAS  Google Scholar 

  4. Furlong EEM, Levine M. Developmental enhancers and chromosome topology. Science. 2018;361:1341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science. 2002;295:1306–11.

    Article  CAS  PubMed  Google Scholar 

  6. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326:289–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li G, Fullwood MJ, Xu H, Mulawadi FH, Velkov S, Vega V, et al. ChIA-PET tool for comprehensive chromatin interaction analysis with paired-end tag sequencing. Genome Biol. 2010;11:R22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Dowen JM, Fan ZP, Hnisz D, Ren G, Abraham BJ, Zhang LN, et al. Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell. 2014;159:374–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hnisz D, Weintraub AS, Day DS, Valton AL, Bak RO, Li CH, et al. Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science. 2016;351:1454–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dixon JR, Jung I, Selvaraj S, Shen Y, Antosiewicz-Bourget JE, Lee AY, et al. Chromatin architecture reorganization during stem cell differentiation. Nature. 2015;518:331–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012;485:376–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ji X, Dadon DB, Powell BE, Fan ZP, Borges-Rivera D, Shachar S, et al. 3D chromosome regulatory landscape of human pluripotent cells. Cell Stem Cell. 2016;18:262–75.

    Article  CAS  PubMed  Google Scholar 

  13. Wu P, Li T, Li R, Jia L, Zhu P, Liu Y, et al. 3D genome of multiple myeloma reveals spatial genome disorganization associated with copy number variations. Nat Commun. 2017;8:1937.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Ptasinska A, Pickin A, Assi SA, Chin PS, Ames L, Avellino R, et al. RUNX1-ETO depletion in t(8;21) AML leads to C/EBPα- and AP-1-mediated alterations in enhancer-promoter interaction. Cell Rep. 2019;28:3022–31.e3027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Speedy HE, Beekman R, Chapaprieta V, Orlando G, Law PJ, Martín-García D, et al. Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics. Nat Commun. 2019;10:3615.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Guo Y, Xu Q, Canzio D, Shou J, Li J, Gorkin DU, et al. CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell. 2015;162:900–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Narendra V, Rocha PP, An D, Raviram R, Skok JA, Mazzoni EO, et al. CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science. 2015;347:1017–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Despang A, Schöpflin R, Franke M, Ali S, Jerković I, Paliou C, et al. Functional dissection of the Sox9–Kcnj2 locus identifies nonessential and instructive roles of TAD architecture. Nat Genet. 2019;51:1263–71.

    Article  CAS  PubMed  Google Scholar 

  19. Kraft K, Magg A, Heinrich V, Riemenschneider C, Schöpflin R, Markowski J, et al. Serial genomic inversions induce tissue-specific architectural stripes, gene misexpression and congenital malformations. Nat Cell Biol. 2019;21:305–10.

    Article  CAS  PubMed  Google Scholar 

  20. Mumbach MR, Satpathy AT, Boyle EA, Dai C, Gowen BG, Cho SW, et al. Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat Genet. 2017;49:1602–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lupiáñez Darío G, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell. 2015;161:1012–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Weischenfeldt J, Dubash T, Drainas AP, Mardin BR, Chen Y, Stütz AM, et al. Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking. Nat Genet. 2017;49:65–74.

    Article  CAS  PubMed  Google Scholar 

  23. Franke M, Ibrahim DM, Andrey G, Schwarzer W, Heinrich V, Schöpflin R, et al. Formation of new chromatin domains determines pathogenicity of genomic duplications. Nature. 2016;538:265–9.

    Article  CAS  PubMed  Google Scholar 

  24. Zhao R, Bodnar MS, Spector DL. Nuclear neighborhoods and gene expression. Curr Opin Genet Dev. 2009;19:172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, et al. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008;453:948–51.

    Article  CAS  PubMed  Google Scholar 

  26. Galeev R, Larsson J. Cohesin in haematopoiesis and leukaemia. Curr Opin Hematol. 2018;25:259–65.

    Article  CAS  PubMed  Google Scholar 

  27. Fisher JB, McNulty M, Burke MJ, Crispino JD, Rao S. Cohesin mutations in myeloid malignancies. Trends Cancer. 2017;3:282–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cuartero S, Merkenschlager M. Three-dimensional genome organization in normal and malignant haematopoiesis. Curr Opin Hematol. 2018;25:323–8.

    Article  CAS  PubMed  Google Scholar 

  29. Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49:1211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ding L-W, Sun Q-Y, Tan K-T, Chien W, Thippeswamy AM, Eng Juh Yeoh A, et al. Mutational landscape of pediatric acute lymphoblastic leukemia. Cancer Res. 2017;77:390.

    Article  CAS  PubMed  Google Scholar 

  31. King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P, et al. The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell. 2013;153:1552–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, et al. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet. 2014;46:364–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Herranz D, Ambesi-Impiombato A, Palomero T, Schnell SA, Belver L, Wendorff AA, et al. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nat Med. 2014;20:1130–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, et al. Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science. 2014;346:1373–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Pinoli P, Stamoulakatou E, Nguyen A-P, Rodríguez Martínez M, Ceri S. Pan-cancer analysis of somatic mutations and epigenetic alterations in insulated neighbourhood boundaries. PLoS ONE. 2020;15:e0227180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Beekman R, Chapaprieta V, Russiñol N, Vilarrasa-Blasi R, Verdaguer-Dot N, Martens JHA, et al. The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia. Nat Med. 2018;24:868–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nasmyth K, Haering CH. Cohesin: its roles and mechanisms. Annu Rev Genet. 2009;43:525–58.

    Article  CAS  PubMed  Google Scholar 

  38. Zhu Z, Wang X. Roles of cohesin in chromosome architecture and gene expression. Semin Cell Developmental Biol. 2019;90:187–93.

    Article  CAS  Google Scholar 

  39. Haarhuis JHI, van der Weide RH, Blomen VA, Yanez-Cuna JO, Amendola M, van Ruiten MS, et al. The cohesin release factor WAPL restricts chromatin loop extension. Cell. 2017;169:693–707.e614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rao SSP, Huang SC, Glenn St Hilaire B, Engreitz JM, Perez EM, Kieffer-Kwon KR, et al. Cohesin loss eliminates all loop domains. Cell. 2017;171:305–20.e324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  42. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N. Engl J Med. 2016;374:2209–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Thol F, Bollin R, Gehlhaar M, Walter C, Dugas M, Suchanek KJ, et al. Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications. Blood. 2014;123:914–20.

    Article  CAS  PubMed  Google Scholar 

  44. Thota S, Viny AD, Makishima H, Spitzer B, Radivoyevitch T, Przychodzen B, et al. Genetic alterations of the cohesin complex genes in myeloid malignancies. Blood. 2014;124:1790–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, et al. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45:1293–9.

    Article  CAS  PubMed  Google Scholar 

  46. Kon A, Shih L-Y, Minamino M, Sanada M, Shiraishi Y, Nagata Y, et al. Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat Genet. 2013;45:1232–7.

    Article  CAS  PubMed  Google Scholar 

  47. Mazumdar C, Shen Y, Xavy S, Zhao F, Reinisch A, Li R, et al. Leukemia-associated cohesin mutants dominantly enforce stem cell programs and impair human hematopoietic progenitor differentiation. Cell Stem Cell. 2015;17:675–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mullenders J, Aranda-Orgilles B, Lhoumaud P, Keller M, Pae J, Wang K, et al. Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms. J Exp Med. 2015;212:1833–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Viny AD, Ott CJ, Spitzer B, Rivas M, Meydan C, Papalexi E, et al. Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis. J Exp Med. 2015;212:1819–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Galeev R, Baudet A, Kumar P, Rundberg Nilsson A, Nilsson B, Soneji S, et al. Genome-wide RNAi screen identifies cohesin genes as modifiers of renewal and differentiation in human HSCs. Cell Rep. 2016;14:2988–3000.

    Article  CAS  PubMed  Google Scholar 

  51. Fisher JB, Peterson J, Reimer M, Stelloh C, Pulakanti K, Gerbec ZJ, et al. The cohesin subunit Rad21 is a negative regulator of hematopoietic self-renewal through epigenetic repression of Hoxa7 and Hoxa9. Leukemia. 2017;31:712–9.

    Article  CAS  PubMed  Google Scholar 

  52. Labuhn M, Perkins K, Matzk S, Varghese L, Garnett C, Papaemmanuil E, et al. Mechanisms of progression of myeloid preleukemia to transformed myeloid leukemia in children with down syndrome. Cancer Cell. 2019;36:123–38.e110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gilliland DG, Jordan CT, Felix CA. The molecular basis of leukemia. Hematol Am Soc Hematol Educ Program. 2004;1:80–97.

    Article  Google Scholar 

  54. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481:506–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012;150:264–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. van der Lelij P, Lieb S, Jude J, Wutz G, Santos CP, Falkenberg K, et al. Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts. eLife. 2017;6:e26980.

  57. Nottingham WT, Jarratt A, Burgess M, Speck CL, Cheng JF, Prabhakar S, et al. Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer. Blood. 2007;110:4188–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ichikawa M, Yoshimi A, Nakagawa M, Nishimoto N, Watanabe-Okochi N, Kurokawa M. A role for RUNX1 in hematopoiesis and myeloid leukemia. Int J Hematol. 2013;97:726–34.

    Article  CAS  PubMed  Google Scholar 

  59. Horsfield JA, Anagnostou SH, Hu JK-H, Cho KHY, Geisler R, Lieschke G, et al. Cohesin-dependent regulation of Runx genes. Development. 2007;134:2639.

    Article  CAS  PubMed  Google Scholar 

  60. Marsman J, O’Neill AC, Kao BR, Rhodes JM, Meier M, Antony J, et al. Cohesin and CTCF differentially regulate spatiotemporal runx1 expression during zebrafish development. Biochim Biophys Acta. 2014;1839:50–61.

    Article  CAS  PubMed  Google Scholar 

  61. Seitan VC, Faure AJ, Zhan Y, McCord RP, Lajoie BR, Ing-Simmons E, et al. Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Genome Res. 2013;23:2066–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ing-Simmons E, Seitan V, Faure A, Flicek P, Carroll T, Dekker J, et al. Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin. Genome Res. 2015;25:504–13.

  63. Cuartero S, Weiss FD, Dharmalingam G, Guo Y, Ing-Simmons E, Masella S, et al. Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation. Nat Immunol. 2018;19:932–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature. 2010;465:793–7. (Electronic).

  65. Pietras EM. Inflammation: a key regulator of hematopoietic stem cell fate in health and disease. Blood. 2017;130:1693–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rao S. Closing the loop on cohesin in hematopoiesis. Blood. 2019;134:2123–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Sasca D, Yun H, Giotopoulos G, Szybinski J, Evan T, Wilson NK, et al. Cohesin-dependent regulation of gene expression during differentiation is lost in Cohesin-mutated myeloid malignancies. Blood. 2019; 134:2195–208.

  68. Viny AD, Bowman RL, Liu Y, Lavallée V-P, Eisman SE, Xiao W, et al. Cohesin members Stag1 and Stag2 display distinct roles in chromatin accessibility and topological control of HSC self-renewal and differentiation. Cell Stem Cell. 2019;25:682–96.e688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Wutz G, Ladurner R, St Hilaire BG, Stocsits RR, Nagasaka K, Pignard B, et al. ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL. eLife. 2020;9:e52091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Casa V, MorontaGines M, Gade Gusmao E, Slotman JA, Zirkel A, Josipovic N, et al. Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcriptional control. Genome Res. 2020;30:515–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC, Calicchio ML, et al. The genomic landscape of pediatric ewing sarcoma. Cancer Discov. 2014;4:1326–41.

    Article  CAS  PubMed  Google Scholar 

  72. Solomon DA, Kim J-S, Bondaruk J, Shariat SF, Wang Z-F, Elkahloun AG, et al. Frequent truncating mutations of STAG2 in bladder cancer. Nat Genet. 2013;45:1428–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Banno K, Omori S, Hirata K, Nawa N, Nakagawa N, Nishimura K, et al. Systematic cellular disease models reveal synergistic interaction of trisomy 21 and GATA1 mutations in hematopoietic abnormalities. Cell Rep. 2016;15:1228–41.

    Article  CAS  PubMed  Google Scholar 

  74. Ochi Y, Kon A, Sakata T, Nakagawa MM, Nakazawa N, Kakuta M, et al. Combined cohesin-runx1 deficiency synergistically perturbs chromatin looping and causes myelodysplastic syndromes. Cancer Discov. 2020;10:1–18.

    Article  Google Scholar 

  75. Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN, Gawad C, et al. Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature. 2018;555:371–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dolnik A, Engelmann JC, Scharfenberger-Schmeer M, Mauch J, Kelkenberg-Schade S, Haldemann B, et al. Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing. Blood. 2012;120:e83–92.

    Article  CAS  PubMed  Google Scholar 

  77. Vicente C, Schwab C, Broux M, Geerdens E, Degryse S, Demeyer S, et al. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia. Haematologica. 2015;100:1301–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kemp Christopher J, Moore James M, Moser R, Bernard B, Teater M, Smith Leslie E, et al. CTCF haploinsufficiency destabilizes DNA methylation and predisposes to cancer. Cell Rep. 2014;7:1020–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yang M, Vesterlund M, Siavelis I, Moura-Castro LH, Castor A, Fioretos T, et al. Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia. Nat Commun. 2019;10:1519.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Wang AJ, Han Y, Jia N, Chen P, Minden MD. NPM1c impedes CTCF functions through cytoplasmic mislocalization in acute myeloid leukemia. Leukemia. 2020;34:1278–90.

    Article  CAS  PubMed  Google Scholar 

  81. Zhang H, Zhu L, He H, Zhu S, Zhang W, Liu X, et al. NF-kappa B mediated up-regulation of CCCTC-binding factor in pediatric acute lymphoblastic leukemia. Mol Cancer. 2014;13:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Maurano Matthew T, Wang H, John S, Shafer A, Canfield T, Lee K, et al. Role of DNA methylation in modulating transcription factor occupancy. Cell Rep. 2015;12:1184–95.

    Article  CAS  PubMed  Google Scholar 

  83. Wang H, Maurano MT, Qu H, Varley KE, Gertz J, Pauli F, et al. Widespread plasticity in CTCF occupancy linked to DNA methylation. Genome Res. 2012;22:1680–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Li Y, Liao Z, Luo H, Benyoucef A, Kang Y, Lai Q, et al. Alteration of CTCF-associated chromatin neighborhood inhibits TAL1-driven oncogenic transcription program and leukemogenesis. Nucleic Acid Res. 2020;48:3119–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zhou Y, Kurukuti S, Saffrey P, Vukovic M, Michie AM, Strogantsev R, et al. Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL. Blood. 2013;122:4199–209.

    Article  CAS  PubMed  Google Scholar 

  86. Uusküla-Reimand L, Hou H, Samavarchi-Tehrani P, Rudan MV, Liang M, Medina-Rivera A, et al. Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders. Genome Biol. 2016;17:182.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Atkin ND, Raimer HM, Wang Y-H. Broken by the cut: a journey into the role of topoisomerase II in DNA fragility. Genes. 2019;10:791.

    Article  CAS  PubMed Central  Google Scholar 

  88. Canela A, Maman Y, Jung S, Wong N, Callen E, Day A, et al. Genome organization drives chromosome fragility. Cell. 2017;170:507–21.e518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Canela A, Maman Y, Huang S-yN, Wutz G, Tang W, Zagnoli-Vieira G. et al. Topoisomerase II-induced chromosome breakage and translocation is determined by chromosome architecture and transcriptional activity. Mol Cell. 2019;75:252–66.e258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Gothe HJ, Bouwman BAM, Gusmao EG, Piccinno R, Petrosino G, Sayols S, et al. Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations. Mol Cell. 2019;75:267–83.e212.

    Article  CAS  PubMed  Google Scholar 

  91. Álvarez-Prado ÁF, Pérez-Durán P, Pérez-García A, Benguria A, Torroja C, de Yébenes VG, et al. A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets. J Exp Med. 2018;215:761–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Akdemir KC, Le VT, Chandran S, Li Y, Verhaak RG, Beroukhim R, et al. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer. Nat Genet. 2020;52:294–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Senigl F, Maman Y, Dinesh RK, Alinikula J, Seth RB, Pecnova L, et al. Topologically associated domains delineate susceptibility to somatic hypermutation. Cell Rep. 2019;29:3902–15.e3908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Prickett AR, Barkas N, McCole RB, Hughes S, Amante SM, Schulz R, et al. Genome-wide and parental allele-specific analysis of CTCF and cohesin DNA binding in mouse brain reveals a tissue-specific binding pattern and an association with imprinted differentially methylated regions. Genome Res. 2013;23:1624–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Hashimoto H, Wang D, Horton JR, Zhang X, Corces VG, Cheng X. Structural basis for the versatile and methylation-dependent binding of CTCF to DNA. Mol Cell. 2017;66:711–20.e713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Rodriguez C, Borgel J, Court F, Cathala G, Forne T, Piette J. CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus. Biochem Biophys Res Commun. 2010;392:129–34.

    Article  CAS  PubMed  Google Scholar 

  97. Feldmann A, Ivanek R, Murr R, Gaidatzis D, Burger L, Schubeler D. Transcription factor occupancy can mediate active turnover of DNA methylation at regulatory regions. PLoS Genet. 2013;9:e1003994.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Lai AY, Fatemi M, Dhasarathy A, Malone C, Sobol SE, Geigerman C, et al. DNA methylation prevents CTCF-mediated silencing of the oncogene BCL6 in B cell lymphomas. J Exp Med. 2010;207:1939–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Kanduri C, Pant V, Loukinov D, Pugacheva E, Qi CF, Wolffe A, et al. Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr Biol. 2000;10:853–6.

    Article  CAS  PubMed  Google Scholar 

  100. Schuijers J, Manteiga JC, Weintraub AS, Day DS, Zamudio AV, Hnisz D, et al. Transcriptional dysregulation of MYC reveals common enhancer-docking mechanism. Cell Rep. 2018;23:349–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Mujahed H, Miliara S, Neddermeyer AH, Bengtzen S, Nilsson C, Deneberg S, et al. AML displays increased CTCF occupancy associated to aberrant gene expression and transcription factor binding. Blood. 2020. https://doi.org/10.1182/blood.2019002326. Online ahead of print.

  102. Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2016;529:110–4.

    Article  CAS  PubMed  Google Scholar 

  103. Flavahan WA, Drier Y, Johnstone SE, Hemming ML, Tarjan DR, Hegazi E, et al. Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs. Nature. 2019;575:229–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Cancer Genome Atlas Research N, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl J Med. 2013;368:2059–74.

    Article  CAS  Google Scholar 

  105. Liu XS, Wu H, Ji X, Stelzer Y, Wu X, Czauderna S, et al. Editing DNA methylation in the mammalian genome. Cell. 2016;167:233–47.e217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Panea RI, Love CL, Shingleton JR, Reddy A, Bailey JA, Moormann AM, et al. The whole-genome landscape of Burkitt lymphoma subtypes. Blood. 2019;134:1598–607.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Kiel MJ, Sahasrabuddhe AA, Rolland DCM, Velusamy T, Chung F, Schaller M, et al. Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome. Nat Commun. 2015;6:8470.

    Article  CAS  PubMed  Google Scholar 

  108. Cheng CK, Li L, Cheng SH, Lau KM, Chan NPH, Wong RSM, et al. Transcriptional repression of the RUNX3/AML2 gene by the t(8;21) and inv(16) fusion proteins in acute myeloid leukemia. Blood. 2008;112:3391–402.

    Article  CAS  PubMed  Google Scholar 

  109. Pulikkan JA, Hegde M, Ahmad HM, Belaghzal H, Illendula A, Yu J, et al. CBFβ-SMMHC inhibition triggers apoptosis by disrupting MYC chromatin dynamics in acute myeloid leukemia. Cell. 2018;174:172–186.e121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Yu M, Mazor T, Huang H, Huang H-T, Kathrein Katie L, Woo Andrew J, et al. Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell. 2012;45:330–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kamikubo Y, Zhao L, Wunderlich M, Corpora T, Hyde RK, Paul TA, et al. Accelerated leukemogenesis by truncated CBF beta-SMMHC defective in high-affinity binding with RUNX1. Cancer Cell. 2010;17:455–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Krivega I, Dean A. LDB1-mediated enhancer looping can be established independent of mediator and cohesin. Nucleic Acids Res. 2017;45:8255–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hewitt KJ, Johnson KD, Gao X, Keles S, Bresnick EH. The hematopoietic stem and progenitor cell cistrome: GATA factor-dependent cis-regulatory mechanisms. Curr Top Dev Biol. 2016;118:45–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Schuetzmann D, Walter C, van Riel B, Kruse S, König T, Erdmann T, et al. Temporal autoregulation during human PU.1 locus SubTAD formation. Blood. 2018;132:2643–55.

    Article  CAS  PubMed  Google Scholar 

  115. Huang Y, Sitwala K, Bronstein J, Sanders D, Dandekar M, Collins C, et al. Identification and characterization of Hoxa9 binding sites in hematopoietic cells. Blood. 2012;119:388–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Collins CT, Hess JL. Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets. Oncogene. 2016;35:1090–8.

    Article  CAS  PubMed  Google Scholar 

  117. Sun Y, Zhou B, Mao F, Xu J, Miao H, Zou Z, et al. HOXA9 reprograms the enhancer landscape to promote leukemogenesis. Cancer Cell. 2018;34:643–658.e645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Narendra V, Rocha PP, An D, Raviram R, Skok JA, Mazzoni EO, et al. CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science. 2015;347:1017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Luo H, Wang F, Zha J, Li H, Yan B, Du Q, et al. CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia. Blood. 2018;132:837–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011;472:120–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Luo H, Zhu G, Xu J, Lai Q, Yan B, Guo Y, et al. HOTTIP lncRNA promotes hematopoietic stem cell self-renewal leading to AML-like disease in mice. Cancer Cell. 2019;36:645–659.e648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Isoda T, Moore AJ, He Z, Chandra V, Aida M, Denholtz M, et al. Non-coding transcription instructs chromatin folding and compartmentalization to dictate enhancer-promoter communication and T cell fate. Cell. 2017;171:103–119.e118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Saldana-Meyer R, Gonzalez-Buendia E, Guerrero G, Narendra V, Bonasio R, Recillas-Targa F, et al. CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53. Genes Dev. 2014;28:723–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Kung JT, Kesner B, An JY, Ahn JY, Cifuentes-Rojas C, Colognori D, et al. Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF. Mol Cell. 2015;57:361–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, et al. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell. 2013;152:727–42.

    Article  CAS  PubMed  Google Scholar 

  126. Northcott PA, Lee C, Zichner T, Stutz AM, Erkek S, Kawauchi D, et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature. 2014;511:428–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Groschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BAM, Erpelinck C, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014;157:369–81.

    Article  CAS  PubMed  Google Scholar 

  128. Yamazaki H, Suzuki M, Otsuki A, Shimizu R, Bresnick EH, Engel JD, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell. 2014;25:415–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Yang M, Safavi S, Woodward EL, Duployez N, Olsson-Arvidsson L, Ungerback J, et al. 13q12.2 deletions in acute lymphoblastic leukemia lead to upregulation of FLT3 through enhancer hijacking. Blood. 2020. https://doi.org/10.1182/blood.2019004684. Online ahead of print.

  130. ar-Rushdi A, Nishikura K, Erikson J, Watt R, Rovera G, Croce CM. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983;222:390–3.

    Article  CAS  PubMed  Google Scholar 

  131. Corces MR, Granja JM, Shams S, Louie BH, Seoane JA, Zhou W, et al. The chromatin accessibility landscape of primary human cancers. Science. 2018;362:eaav1898.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Valencia AM, Kadoch C. Chromatin regulatory mechanisms and therapeutic opportunities in cancer. Nat Cell Biol. 2019;21:152–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Wong RWJ, Ngoc PCT, Leong WZ, Yam AWY, Zhang T, Asamitsu K, et al. Enhancer profiling identifies critical cancer genes and characterizes cell identity in adult T-cell leukemia. Blood. 2017;130:2326–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Polak P, Karlić R, Koren A, Thurman R, Sandstrom R, Lawrence MS, et al. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature. 2015;518:360–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. George J, Uyar A, Young K, Kuffler L, Waldron-Francis K, Marquez E, et al. Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells. Nat Commun. 2016;7:12166.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Shi J, Whyte WA, Zepeda-Mendoza CJ, Milazzo JP, Shen C, Roe J-S, et al. Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation. Genes Dev. 2013;27:2648–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Heshmati Y, Türköz G, Harisankar A, Kharazi S, Boström J, Dolatabadi EK, et al. The chromatin-remodeling factor CHD4 is required for maintenance of childhood acute myeloid leukemia. Haematologica. 2018;103:1169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Gozdecka M, Meduri E, Mazan M, Tzelepis K, Dudek M, Knights AJ, et al. UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs. Nat Genet. 2018;50:883–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Rodríguez D, Bretones G, Quesada V, Villamor N, Arango JR, López-Guillermo A, et al. Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia. Blood. 2015;126:195–202.

    Article  PubMed  CAS  Google Scholar 

  140. Kulkarni S, Nagarajan P, Wall J, Donovan DJ, Donell RL, Ligon AH, et al. Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis. Am J Med Genet Part A. 2008;146A:1117–27.

    Article  CAS  PubMed  Google Scholar 

  141. Masetti R, Biagi C, Zama D, Vendemini F, Martoni A, Morello W, et al. Retinoids in pediatric onco-hematology: the model of acute promyelocytic leukemia and neuroblastoma. Adv Ther. 2012;29:747–62.

    Article  CAS  PubMed  Google Scholar 

  142. Nichol Jessica N, Galbraith Matthew D, Kleinman Claudia L, Espinosa Joaquín M, Miller Wilson H Jr. NPM and BRG1 mediate transcriptional resistance to retinoic acid in acute promyelocytic leukemia. Cell Rep. 2016;14:2938–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Ooi L, Belyaev ND, Miyake K, Wood IC, Buckley NJ. BRG1 chromatin remodeling activity is required for efficient chromatin binding by repressor element 1-silencing transcription factor (REST) and facilitates REST-mediated repression. J Biol Chem. 2006;281:38974–80.

    Article  CAS  PubMed  Google Scholar 

  144. Pal S, Yun R, Datta A, Lacomis L, Erdjument-Bromage H, Kumar J, et al. mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the myc target gene cad. Mol Cell Biol. 2003;23:7475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Witzel M, Petersheim D, Fan Y, Bahrami E, Racek T, Rohlfs M, et al. Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes. Nat Genet. 2017;49:742–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Han L, Madan V, Mayakonda A, Dakle P, Woon TW, Shyamsunder P, et al. Chromatin remodeling mediated by ARID1A is indispensable for normal hematopoiesis in mice. Leukemia. 2019;33:2291–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Guryanova OA, Shank K, Spitzer B, Luciani L, Koche RP, Garrett-Bakelman FE, et al. DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling. Nat Med. 2016;22:1488–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Volk A, Liang K, Suraneni P, Li X, Zhao J, Bulic M, et al. A CHAF1B-dependent molecular switch in hematopoiesis and leukemia pathogenesis. Cancer Cell. 2018;34:707–723.e707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Cheloufi S, Elling U, Hopfgartner B, Jung YL, Murn J, Ninova M, et al. The histone chaperone CAF-1 safeguards somatic cell identity. Nature. 2015;528:218–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Aster JC, Pear WS, Blacklow SC. The varied roles of notch in cancer. Annu Rev Pathol. 2017;12:245–75.

    Article  CAS  PubMed  Google Scholar 

  151. Petrovic J, Zhou Y, Fasolino M, Goldman N, Schwartz GW, Mumbach MR, et al. Oncogenic notch promotes long-range regulatory interactions within hyperconnected 3D cliques. Mol Cell. 2019;73:1174–1190.e1112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Yashiro-Ohtani Y, Wang H, Zang C, Arnett KL, Bailis W, Ho Y, et al. Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia. Proc Natl Acad Sci USA. 2014;111:E4946–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Belver L, Yang AY, Albero R, Herranz D, Brundu FG, Quinn SA, et al. GATA3-controlled nucleosome eviction drives MYC enhancer activity in T-cell development and leukemia. Cancer Discov. 2019;9:1774–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, Margolin A, et al. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci USA. 2006;103:18261–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Kloetgen A, Thandapani P, Ntziachristos P, Ghebrechristos Y, Nomikou S, Lazaris C, et al. Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia. Nat Genet. 2020;52:388–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Rosencrance CD, Ammouri HN, Yu Q, Ge T, Rendleman EJ, Marshall SA, et al. Chromatin hyperacetylation impacts chromosome folding by forming a nuclear subcompartment. Mol Cell. 2020;78:112–126.e112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Huang Y, Mouttet B, Warnatz H-J, Risch T, Rietmann F, Frommelt F, et al. The leukemogenic TCF3-HLF complex rewires enhancers driving cellular identity and self-renewal conferring EP300 vulnerability. Cancer Cell. 2019;36:630–644.e639.

    Article  CAS  PubMed  Google Scholar 

  158. Bahr C, von Paleske L, Uslu VV, Remeseiro S, Takayama N, Ng SW, et al. A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies. Nature. 2018;553:515–20.

    Article  CAS  PubMed  Google Scholar 

  159. Hyle J, Zhang Y, Wright S, Xu B, Shao Y, Easton J, et al. Acute depletion of CTCF directly affects MYC regulation through loss of enhancer–promoter looping. Nucleic Acids Res. 2019;47:6699–713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014;511:616–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146:904–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This review was supported in part by the NIH (CA101774 to JDC, R01CA248770 and U54CA193419 to PN, and 5T32GM008152-33 to CF by the NIH-NIGMS training grant), the NSF (1830968 (PN) and the Zell Foundation (to PN).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Celestia Fang, John D. Crispino & Panagiotis Ntziachristos

  2. Versiti Blood Research Institute, Milwaukee, WI, 53226, USA

    Sridhar Rao

  3. Division of Hematology, Northwestern University, Chicago, IL, 60611, USA

    John D. Crispino & Panagiotis Ntziachristos

  4. Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    John D. Crispino & Panagiotis Ntziachristos

  5. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA

    John D. Crispino & Panagiotis Ntziachristos

Authors
  1. Celestia Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sridhar Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John D. Crispino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Panagiotis Ntziachristos
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CF, SR, JDC, and PN wrote the review.

Corresponding authors

Correspondence to John D. Crispino or Panagiotis Ntziachristos.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fang, C., Rao, S., Crispino, J.D. et al. Determinants and role of chromatin organization in acute leukemia. Leukemia 34, 2561–2575 (2020). https://doi.org/10.1038/s41375-020-0981-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-020-0981-z

This article is cited by

Search

Advanced search

Quick links