Top

Published in:

Open Access 01-12-2014 | Review

Cohesin mutations in myeloid malignancies: underlying mechanisms

Authors: Bryony Leeke, Judith Marsman, Justin M O’Sullivan, Julia A Horsfield

Published in: Experimental Hematology & Oncology | Issue 1/2014

Abstract

Recently, whole genome sequencing approaches have pinpointed mutations in genes that were previously not associated with cancer. For Acute Myeloid Leukaemia (AML), and other myeloid disorders, these approaches revealed a high prevalence of mutations in genes encoding the chromosome cohesion complex, cohesin. Cohesin mutations represent a novel genetic pathway for AML, but how AML arises from these mutations is unknown. This review will explore the potential mechanisms by which cohesin mutations contribute to AML and other myeloid malignancies.

Available only for authorised users

Betz BL, Hess JL: Acute myeloid leukemia diagnosis in the 21st century. Arch Pathol Lab Med 2010, 134: 1427–1433.PubMed

Sanders MA, Valk PJ: The evolving molecular genetic landscape in acute myeloid leukaemia. Curr Opin Hematol 2013, 20: 79–85. 10.1097/MOH.0b013e32835d821cPubMedCrossRef

Ball AR Jr, Chen YY, Yokomori K: Mechanisms of cohesin-mediated gene regulation and lessons learned from cohesinopathies. Biochim Biophys Acta 2014, 1839: 191–202. 10.1016/j.bbagrm.2013.11.002PubMedCentralPubMedCrossRef

Bose T, Gerton JL: Cohesinopathies, gene expression, and chromatin organization. J Cell Biol 2010, 189: 201–210. 10.1083/jcb.200912129PubMedCentralPubMedCrossRef

Horsfield JA, Print CG, Monnich M: Diverse developmental disorders from the one ring: distinct molecular pathways underlie the cohesinopathies. Front Genet 2012, 3: 171.PubMedCentralPubMedCrossRef

Merkenschlager M, Odom DT: CTCF and cohesin: linking gene regulatory elements with their targets. Cell 2013, 152: 1285–1297. 10.1016/j.cell.2013.02.029PubMedCrossRef

Nasmyth K, Haering CH: Cohesin: its roles and mechanisms. Annu Rev Genet 2009, 43: 525–558. 10.1146/annurev-genet-102108-134233PubMedCrossRef

Skibbens RV, Colquhoun JM, Green MJ, Molnar CA, Sin DN, Sullivan BJ, Tanzosh EE: Cohesinopathies of a feather flock together. PLoS Genet 2013, 9: e1004036. 10.1371/journal.pgen.1004036PubMedCentralPubMedCrossRef

Wu N, Yu H: The Smc complexes in DNA damage response. Cell Biosci 2012, 2: 5. 10.1186/2045-3701-2-5PubMedCentralPubMedCrossRef

10.

Dorsett D, Strom L: The ancient and evolving roles of cohesin in gene expression and DNA repair. Curr Biol 2012, 22: R240-R250. 10.1016/j.cub.2012.02.046PubMedCentralPubMedCrossRef

11.

Dorsett D, Krantz ID: On the molecular etiology of Cornelia de Lange syndrome. Ann N Y Acad Sci 2009, 1151: 22–37. 10.1111/j.1749-6632.2008.03450.xPubMedCentralPubMedCrossRef

12.

Rhodes JM, McEwan M, Horsfield JA: Gene regulation by cohesin in cancer: is the ring an unexpected party to proliferation? Mol Cancer Res 2011, 9: 1587–1607. 10.1158/1541-7786.MCR-11-0382PubMedCrossRef

13.

Xu H, Tomaszewski JM, McKay MJ: Can corruption of chromosome cohesion create a conduit to cancer? Nat Rev Cancer 2011, 11: 199–210. 10.1038/nrc3018PubMedCrossRef

14.

Taylor CF, Platt FM, Hurst CD, Thygesen HH, Knowles MA: Frequent inactivating mutations of STAG2 in bladder cancer are associated with low tumour grade and stage and inversely related to chromosomal copy number changes. Hum Mol Genet 2014, 23: 1964–1974. 10.1093/hmg/ddt589PubMedCentralPubMedCrossRef

15.

Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L: Mutational landscape and significance across 12 major cancer types. Nature 2013, 502: 333–339. 10.1038/nature12634PubMedCentralPubMedCrossRef

16.

Barber TD, McManus K, Yuen KW, Reis M, Parmigiani G, Shen D, Barrett I, Nouhi Y, Spencer F, Markowitz S, Velculescu VE, Kinzler KW, Vogelstein B, Lengauer C, Hieter P: Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc Natl Acad Sci U S A 2008, 105: 3443–3448. 10.1073/pnas.0712384105PubMedCentralPubMedCrossRef

17.

Xu H, Yan M, Patra J, Natrajan R, Yan Y, Swagemakers S, Tomaszewski JM, Verschoor S, Millar EK, van der Spek P, Reis-Filho JS, Ramsay RG, O'Toole SA, McNeil CM, Sutherland RL, McKay MJ, Fox SB: Enhanced RAD21 cohesin expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers. Breast Cancer Res 2011, 13: R9. 10.1186/bcr2814PubMedCentralPubMedCrossRef

18.

Vass S, Cotterill S, Valdeolmillos AM, Barbero JL, Lin E, Warren WD, Heck MM: Depletion of Drad21/Scc1 in Drosophila cells leads to instability of the cohesin complex and disruption of mitotic progression. Curr Biol 2003, 13: 208–218. 10.1016/S0960-9822(03)00047-2PubMedCrossRef

19.

Rollins RA, Korom M, Aulner N, Martens A, Dorsett D: Drosophila nipped-B protein supports sister chromatid cohesion and opposes the stromalin/Scc3 cohesion factor to facilitate long-range activation of the cut gene. Mol Cell Biol 2004, 24: 3100–3111. 10.1128/MCB.24.8.3100-3111.2004PubMedCentralPubMedCrossRef

20.

Cancer Genome Atlas Research N: Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013, 368: 2059–2074.CrossRef

21.

Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, Wartman LD, Lamprecht TL, Liu F, Xia J, Kandoth C, Fulton RS, McLellan MD, Dooling DJ, Wallis JW, Chen K, Harris CC, Schmidt HK, Kalicki-Veizer JM, Lu C, Zhang Q, Lin L, O'Laughlin MD, McMichael JF, Delehaunty KD, Fulton LA, Magrini VJ, McGrath SD, Demeter RT, Vickery TL, et al.: The origin and evolution of mutations in acute myeloid leukemia. Cell 2012, 150: 264–278. 10.1016/j.cell.2012.06.023PubMedCentralPubMedCrossRef

22.

Rocquain J, Gelsi-Boyer V, Adelaide J, Murati A, Carbuccia N, Vey N, Birnbaum D, Mozziconacci MJ, Chaffanet M: Alteration of cohesin genes in myeloid diseases. Am J Hematol 2010, 85: 717–719. 10.1002/ajh.21798PubMedCrossRef

23.

Jan M, Snyder TM, Corces-Zimmerman MR, Vyas P, Weissman IL, Quake SR, Majeti R: Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci Transl Med 2012, 4: 149. ra118CrossRef

24.

Thol F, Bollin R, Gehlhaar M, Walter C, Dugas M, Suchanek KJ, Kirchner A, Huang L, Chaturvedi A, Wichmann M, Wiehlmann L, Shahswar R, Damm F, Gohring G, Schlegelberger B, Schlenk R, Dohner K, Dohner H, Krauter J, Ganser A, Heuser M: Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications. Blood 2014, 123: 914–920. 10.1182/blood-2013-07-518746PubMedCrossRef

25.

Kon A, Shih LY, Minamino M, Sanada M, Shiraishi Y, Nagata Y, Yoshida K, Okuno Y, Bando M, Nakato R, Ishikawa S, Sato-Otsubo A, Nagae G, Nishimoto A, Haferlach C, Nowak D, Sato Y, Alpermann T, Nagasaki M, Shimamura T, Tanaka H, Chiba K, Yamamoto R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Nakamaki T, Ishiyama K, Nolte F, et al.: Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat Genet 2013, 45: 1232–1237. 10.1038/ng.2731PubMedCrossRef

26.

Kihara R, Nagata Y, Kiyoi H, Kato T, Yamamoto E, Suzuki K, Chen F, Asou N, Ohtake S, Miyawaki S, Miyazaki Y, Sakura T, Ozawa Y, Usui N, Kanamori H, Kiguchi T, Imai K, Uike N, Kimura F, Kitamura K, Nakaseko C, Onizuka M, Takeshita A, Ishida F, Suzushima H, Kato Y, Miwa H, Shiraishi Y, Chiba K, Tanaka H, et al.: Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 2014. doi:10.1038/leu.2014.55. [Epub ahead of print]

27.

Dolnik A, Engelmann JC, Scharfenberger-Schmeer M, Mauch J, Kelkenberg-Schade S, Haldemann B, Fries T, Kronke J, Kuhn MW, Paschka P, Kayser S, Wolf S, Gaidzik VI, Schlenk RF, Rucker FG, Dohner H, Lottaz C, Dohner K, Bullinger L: Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing. Blood 2012, 120: e83-e92. 10.1182/blood-2011-12-401471PubMedCrossRef

28.

Walter MJ, Shen D, Shao J, Ding L, White BS, Kandoth C, Miller CA, Niu B, McLellan MD, Dees ND, Fulton R, Elliot K, Heath S, Grillot M, Westervelt P, Link DC, DiPersio JF, Mardis E, Ley TJ, Wilson RK, Graubert TA: Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia 2013, 27: 1275–1282. 10.1038/leu.2013.58PubMedCentralPubMedCrossRef

29.

Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, Schnittger S, Sanada M, Kon A, Alpermann T, Yoshida K, Roller A, Nadarajah N, Shiraishi Y, Shiozawa Y, Chiba K, Tanaka H, Koeffler HP, Klein HU, Dugas M, Aburatani H, Kohlmann A, Miyano S, Haferlach C, Kern W, Ogawa S: Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014, 28: 241–247. 10.1038/leu.2013.336PubMedCentralPubMedCrossRef

30.

Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, Sanada M, Park MJ, Terui K, Suzuki H, Kon A, Nagata Y, Sato Y, Wang R, Shiba N, Chiba K, Tanaka H, Hama A, Muramatsu H, Hasegawa D, Nakamura K, Kanegane H, Tsukamoto K, Adachi S, Kawakami K, Kato K, Nishimura R, Izraeli S, Hayashi Y, Miyano S, et al.: The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet 2013, 45: 1293–1299. 10.1038/ng.2759PubMedCrossRef

31.

Solomon DA, Kim JS, Bondaruk J, Shariat SF, Wang ZF, Elkahloun AG, Ozawa T, Gerard J, Zhuang D, Zhang S, Navai N, Siefker-Radtke A, Phillips JJ, Robinson BD, Rubin MA, Volkmer B, Hautmann R, Kufer R, Hogendoorn PC, Netto G, Theodorescu D, James CD, Czerniak B, Miettinen M, Waldman T: Frequent truncating mutations of STAG2 in bladder cancer. Nat Genet 2013, 45: 1428–1430. 10.1038/ng.2800PubMedCrossRef

32.

Guo G, Sun X, Chen C, Wu S, Huang P, Li Z, Dean M, Huang Y, Jia W, Zhou Q, Tang A, Yang Z, Li X, Song P, Zhao X, Ye R, Zhang S, Lin Z, Qi M, Wan S, Xie L, Fan F, Nickerson ML, Zou X, Hu X, Xing L, Lv Z, Mei H, Gao S, Liang C, et al.: Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat Genet 2013, 45: 1459–1463. 10.1038/ng.2798PubMedCrossRef

33.

Balbas-Martinez C, Sagrera A, Carrillo-de-Santa-Pau E, Earl J, Marquez M, Vazquez M, Lapi E, Castro-Giner F, Beltran S, Bayes M, Carrato A, Cigudosa JC, Dominguez O, Gut M, Herranz J, Juanpere N, Kogevinas M, Langa X, Lopez-Knowles E, Lorente JA, Lloreta J, Pisano DG, Richart L, Rico D, Salgado RN, Tardon A, Chanock S, Heath S, Valencia A, Losada A, et al.: Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy. Nat Genet 2013, 45: 1464–1469. 10.1038/ng.2799PubMedCrossRef

34.

Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, Ebmeier CC, Goossens J, Rahl PB, Levine SS, Taatjes DJ, Dekker J, Young RA: Mediator and cohesin connect gene expression and chromatin architecture. Nature 2010, 467: 430–435. 10.1038/nature09380PubMedCentralPubMedCrossRef

35.

Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B: Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 2012, 485: 376–380. 10.1038/nature11082PubMedCentralPubMedCrossRef

36.

Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J: Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 2009, 326: 289–293. 10.1126/science.1181369PubMedCentralPubMedCrossRef

37.

Li Y, Huang W, Niu L, Umbach DM, Covo S, Li L: Characterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes. BMC Genomics 2013, 14: 553. 10.1186/1471-2164-14-553PubMedCentralPubMedCrossRef

38.

Seitan V, Faure A, Zhan Y, McCord R, Lajoie B, Ing-Simmons E, Lenhard B, Giorgetti L, Heard E, Fisher A, Flicek P, Dekker J, Merkenschlager M: Cohesin-based chromatin interactions enable regulated gene expression within pre-existing architectural compartments. Genome Res 2013, 23: 2066–2077. 10.1101/gr.161620.113PubMedCentralPubMedCrossRef

39.

Sofueva S, Yaffe E, Chan W-C, Georgopoulou D, Vietri Rudan M, Mira-Bontenbal H, Pollard SM, Schroth GP, Tanay A, Hadjur S: Cohesin-mediated interactions organize chromosomal domain architecture. EMBO J 2013, 32: 3119–3129. 10.1038/emboj.2013.237PubMedCentralPubMedCrossRef

40.

Zuin J, Dixon JR, van der Reijden MI, Ye Z, Kolovos P, Brouwer RW, van de Corput MP, van de Werken HJ, Knoch TA, van Ijcken WF, Grosveld FG, Ren B, Wendt KS: Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci U S A 2014, 111: 996–1001. 10.1073/pnas.1317788111PubMedCentralPubMedCrossRef

41.

Stedman W, Kang H, Lin S, Kissil JL, Bartolomei MS, Lieberman PM: Cohesins localize with CTCF at the KSHV latency control region and at cellular c-myc and H19/Igf2 insulators. EMBO J 2008, 27: 654–666. 10.1038/emboj.2008.1PubMedCentralPubMedCrossRef

42.

Wendt KS, Yoshida K, Itoh T, Bando M, Koch B, Schirghuber E, Tsutsumi S, Nagae G, Ishihara K, Mishiro T, Yahata K, Imamoto F, Aburatani H, Nakao M, Imamoto N, Maeshima K, Shirahige K, Peters JM: Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 2008, 451: 796–801. 10.1038/nature06634PubMedCrossRef

43.

Parelho V, Hadjur S, Spivakov M, Leleu M, Sauer S, Gregson HC, Jarmuz A, Canzonetta C, Webster Z, Nesterova T, Cobb BS, Yokomori K, Dillon N, Aragon L, Fisher AG, Merkenschlager M: Cohesins Functionally Associate with CTCF on Mammalian Chromosome Arms. Cell 2008, 132: 422–433. 10.1016/j.cell.2008.01.011PubMedCrossRef

44.

Faure AJ, Schmidt D, Watt S, Schwalie PC, Wilson MD, Xu H, Ramsay RG, Odom DT, Flicek P: Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules. Genome Res 2012, 22: 2163–2175. 10.1101/gr.136507.111PubMedCentralPubMedCrossRef

45.

Schmidt D, Schwalie P, Ross-Innes CS, Hurtado A, Brown G, Carroll J, Flicek P, Odom D: A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res 2010, 20: 578–588. 10.1101/gr.100479.109PubMedCentralPubMedCrossRef

46.

Dorsett D, Merkenschlager M: Cohesin at active genes: a unifying theme for cohesin and gene expression from model organisms to humans. Curr Opin Cell Biol 2013,25(3):327–333. 10.1016/j.ceb.2013.02.003PubMedCentralPubMedCrossRef

47.

Kawauchi S, Calof AL, Santos R, Lopez-Burks ME, Young CM, Hoang MP, Chua A, Lao T, Lechner MS, Daniel JA, Nussenzweig A, Kitzes L, Yokomori K, Hallgrimsson B, Lander AD: Multiple organ system defects and transcriptional dysregulation in the Nipbl(+/-) mouse, a model of Cornelia de Lange Syndrome. PLoS Genet 2009, 5: e1000650. 10.1371/journal.pgen.1000650PubMedCentralPubMedCrossRef

48.

Liu J, Feldman R, Zhang Z, Deardorff MA, Haverfield EV, Kaur M, Li JR, Clark D, Kline AD, Waggoner DJ, Das S, Jackson LG, Krantz ID: SMC1A expression and mechanism of pathogenicity in probands with X-Linked Cornelia de Lange syndrome. Hum Mutat 2009, 30: 1535–1542. 10.1002/humu.21095PubMedCentralPubMedCrossRef

49.

Dorsett D, Eissenberg JC, Misulovin Z, Martens A, Redding B, McKim K: Effects of sister chromatid cohesion proteins on cut gene expression during wing development in Drosophila. Development 2005, 132: 4743–4753. 10.1242/dev.02064PubMedCentralPubMedCrossRef

50.

Schaaf CA, Misulovin Z, Sahota G, Siddiqui AM, Schwartz YB, Kahn TG, Pirrotta V, Gause M, Dorsett D: Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins. PLoS ONE 2009, 4: e6202. 10.1371/journal.pone.0006202PubMedCentralPubMedCrossRef

51.

Zhou Y, Kurukuti S, Saffrey P, Vukovic M, Michie AM, Strogantsev R, West AG, Vetrie D: Chromatin looping defines expression of TAL1, its flanking genes and regulation in T-ALL. Blood 2013, 122: 4199–4209. 10.1182/blood-2013-02-483875PubMedCrossRef

52.

Gao X, Johnson KD, Chang YI, Boyer ME, Dewey CN, Zhang J, Bresnick EH: Gata2 cis-element is required for hematopoietic stem cell generation in the mammalian embryo. J Exp Med 2013, 210: 2833–2842. 10.1084/jem.20130733PubMedCentralPubMedCrossRef

53.

Diffner E, Beck D, Gudgin E, Thoms JA, Knezevic K, Pridans C, Foster S, Goode D, Lim WK, Boelen L, Metzeler KH, Micklem G, Bohlander SK, Buske C, Burnett A, Ottersbach K, Vassiliou GS, Olivier J, Wong JW, Gottgens B, Huntly BJ, Pimanda JE: Activity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia. Blood 2013, 121: 2289–2300. 10.1182/blood-2012-07-446120PubMedCrossRef

54.

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 U S A 1996, 93: 3444–3449. 10.1073/pnas.93.8.3444PubMedCentralPubMedCrossRef

55.

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: 321–330. 10.1016/S0092-8674(00)80986-1PubMedCrossRef

56.

Schlegelberger B, Gohring G, Thol F, Heuser M: Update on cytogenetic and molecular changes in myelodysplastic syndromes. Leuk Lymphoma 2012, 53: 525–536. 10.3109/10428194.2011.618235PubMedCrossRef

57.

Horsfield JA, Anagnostou SH, Hu JK, Cho KH, Geisler R, Lieschke G, Crosier KE, Crosier PS: Cohesin-dependent regulation of Runx genes. Development 2007, 134: 2639–2649. 10.1242/dev.002485PubMedCrossRef

58.

Nottingham WT, Jarratt A, Burgess M, Speck CL, Cheng JF, Prabhakar S, Rubin EM, Li PS, Sloane-Stanley J, Kong ASJ, de Bruijn MF: Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer. Blood 2007, 110: 4188–4197. 10.1182/blood-2007-07-100883PubMedCentralPubMedCrossRef

59.

Ng CE, Yokomizo T, Yamashita N, Cirovic B, Jin H, Wen Z, Ito Y, Osato M: A Runx1 intronic enhancer marks hemogenic endothelial cells and hematopoietic stem cells. Stem Cells 2010, 28: 1869–1881. 10.1002/stem.507PubMedCrossRef

60.

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

61.

Li G, Ruan X, Auerbach RK, Sandhu KS, Zheng M, Wang P, Poh HM, Goh Y, Lim J, Zhang J, Sim HS, Peh SQ, Mulawadi FH, Ong CT, Orlov YL, Hong S, Zhang Z, Landt S, Raha D, Euskirchen G, Wei CL, Ge W, Wang H, Davis C, Fisher-Aylor KI, Mortazavi A, Gerstein M, Gingeras T, Wold B, Sun Y, et al.: Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 2012, 148: 84–98. 10.1016/j.cell.2011.12.014PubMedCentralPubMedCrossRef

62.

Panigrahi AK, Pati D: Higher-order orchestration of hematopoiesis: is cohesin a new player? Exp Hematol 2012, 40: 967–973. 10.1016/j.exphem.2012.09.010PubMedCentralPubMedCrossRef

63.

Yan J, Enge M, Whitington T, Dave K, Liu J, Sur I, Schmierer B, Jolma A, Kivioja T, Taipale M, Taipale J: Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites. Cell 2013, 154: 801–813. 10.1016/j.cell.2013.07.034PubMedCrossRef

Title: Cohesin mutations in myeloid malignancies: underlying mechanisms
Authors: Bryony Leeke
Judith Marsman
Justin M O’Sullivan
Julia A Horsfield
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Experimental Hematology & Oncology / Issue 1/2014
Electronic ISSN: 2162-3619
DOI: https://doi.org/10.1186/2162-3619-3-13

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

Vitamin D3 potentiates the antitumorigenic effects of arsenic trioxide in human leukemia (HL-60) cells

Comparative study of the effect of rivaroxaban and fondaparinux on monocyte’s coagulant activity and cytokine release

Salvage therapy with high dose Intravenous Immunoglobulins in acquired Von Willebrand Syndrome and unresponsive severe intestinal bleeding

Modulation of deoxycytidine kinase (dCK) and glycogen synthase kinase (GSK-3β) by anti-CD20 (rituximab) and 2-chlorodeoxyadenosine (2-CdA) in human lymphoid malignancies

Epidemiologic study of myelodysplastic syndromes in a multiethnic, inner city cohort

Expression and diagnostic values of calretinin and CK5/6 in cholangiocarcinoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer