In focus: MLL-rearranged leukemia

Leukemia

Volumn 27, Issue 6, 2013, Pages 1224-1228

  De Boer, J ^a   Walf Vorderwulbecke V ^a   Williams, O ^a  

^a GREAT ORMOND STREET HOSPITAL   (United Kingdom)

Author keywords

ALL; AML; leukemia; MLL

Indexed keywords

4 AMINO 7 TERT BUTYL 5 (4 CHLOROPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; HISTONE DEACETYLASE INHIBITOR; HYBRID PROTEIN; LENS EPITHELIUM DERIVED GROWTH FACTOR; METHIONINE; MICRORNA; MIXED LINEAGE LEUKEMIA PROTEIN; MULTIPROTEIN COMPLEX; SOMATOMEDIN C RECEPTOR; TRANSCRIPTION FACTOR JUND;

COLONY FORMATION; ENZYME PHOSPHORYLATION; EPIGENETICS; FUSION GENE; GENE MUTATION; HUMAN; LEUKEMIA; LEUKEMIA CELL; LEUKEMOGENESIS; PRIORITY JOURNAL; REVIEW;

EPIGENESIS, GENETIC; GENE REARRANGEMENT; HUMANS; LEUKEMIA; MICRORNAS; MUTATION; MYELOID-LYMPHOID LEUKEMIA PROTEIN;

EID: 84878926218     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2013.78     Document Type: Review

References (82)

1. Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa 3rd R, Patel Y, Harden A et al. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci USA 1991; 88: 10735-10739. (Pubitemid 21915912)
2. Cimino G, Moir DT, Canaani O, Williams K, Crist WM, Katzav S et al. Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res 1991; 51: 6712-6714.
3. Yu BD, Hess JL, Horning SE, Brown GA, Korsmeyer SJ. Altered Hox expression and segmental identity in Mll-mutant mice. Nature 1995; 378: 505-508.
4. Yano T, Nakamura T, Blechman J, Sorio C, Dang CV, Geiger B et al. Nuclear punctate distribution of ALL-1 is conferred by distinct elements at the N terminus of the protein. Proc Natl Acad Sci USA 1997; 94: 7286-7291. (Pubitemid 27345307)
5. Gould A. Functions of mammalian polycomb group and trithorax group related genes. Curr Opin Genet Dev 1997; 7: 488-494. (Pubitemid 27404279)
6. 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.
7. Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G 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: 701-708.
8. Mueller D, Bach C, Zeisig D, Garcia-Cuellar MP, Monroe S, Sreekumar A et al. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 2007; 110: 4445-4454. (Pubitemid 351377811)
9. Mueller D, Garcia-Cuellar MP, Bach C, Buhl S, Maethner E, Slany RK. Misguided transcriptional elongation causes mixed lineage leukemia. PLoS Biol 2009; 7: e1000249.
10. Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary ML. A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell 2010; 17: 198-212.
11. Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L et al. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell 2010; 37: 429-437.
12. Slany RK. The molecular biology of mixed lineage leukemia. Haematologica 2009; 94: 984-993.
13. Mohan M, Lin C, Guest E, Shilatifard A. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat Rev Cancer 2010; 10: 721-728.
14. Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev 2011; 25: 661-672.
15. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero DJ, Kitabayashi I et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol 2004; 24: 5639-5649. (Pubitemid 38787950)
16. Milne TA, Hughes CM, Lloyd R, Yang Z, Rozenblatt-Rosen O, Dou Y et al. Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors. Proc Natl Acad Sci USA 2005; 102: 749-754. (Pubitemid 40282737)
17. Yokoyama A, Cleary ML. Menin critically links MLL proteins with LEDGF on cancerassociated target genes. Cancer Cell 2008; 14: 36-46. (Pubitemid 351885493)
18. Yokoyama A, Somervaille TC, Smith KS, Rozenblatt-Rosen O, Meyerson M, Cleary ML. The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell 2005; 123: 207-218. (Pubitemid 41457212)
19. Caslini C, Yang Z, El-Osta M, Milne TA, Slany RK, Hess JL. Interaction of MLL amino terminal sequences with menin is required for transformation. Cancer Res 2007; 67: 7275-7283. (Pubitemid 47206556)
20. Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K et al. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature 2012; 482: 542-546.
21. Mereau H, De Rijck J, Cermakova K, Kutz A, Juge S, Demeulemeester J et al. Impairing MLL-fusion gene mediated transformation by dissecting critical interactions with the lens epithelium-derived growth factor (LEDGF/p75). Leukemia 2013; e-pub ahead of print 15 January 2013; doi:10.1038/leu.2013.10.
22. Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia. Nature 2011; 478 529-533
23. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukemia. Nature 2011; 478: 524-528.
24. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM et al. hDOT1L links histone methylation to leukemogenesis. Cell 2005; 121: 167-178. (Pubitemid 40546386)
25. Krivtsov AV, Feng Z, Lemieux ME, Faber J, Vempati S, Sinha AU et al. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell 2008; 14: 355-368.
26. Chang MJ, Wu H, Achille NJ, Reisenauer MR, Chou CW, Zeleznik-Le NJ et al. Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer Res 2010; 70: 10234-10242.
27. Jo SY, Granowicz EM, Maillard I, Thomas D, Hess JL. Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation. Blood 2011; 117: 4759-4768.
28. Nguyen AT, Taranova O, He J, Zhang Y. DOT1L, the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis. Blood 2011; 117: 6912-6922.
29. Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 2011; 20: 66-78.
30. Garcia-Cuellar MP, Zilles O, Schreiner SA, Birke M, Winkler TH, Slany RK. The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human polycomb 3. Oncogene 2001; 20: 411-419. (Pubitemid 32158221)
31. Hemenway CS, de Erkenez AC, Gould GC. The polycomb protein MPc3 interacts with AF9, an MLL fusion partner in t(9;11)(p22;q23) acute leukemias. Oncogene 2001; 20: 3798-3805. (Pubitemid 32646190)
32. Tan J, Jones M, Koseki H, Nakayama M, Muntean AG, Maillard I et al. CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis. Cancer Cell 2011; 20: 563-575.
33. Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia 2012; e-pub ahead of print 9 November 2012; doi:10.1038/leu.2012.327.
34. Deshpande AJ, Chen L, Fazio M, Sinha AU, Bernt KM, Banka D et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood 2013; 121: 2533-2541.
35. Harris WJ, Huang X, Lynch JT, Spencer GJ, Hitchin JR, Li Y et al. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 2012; 21: 473-487.
36. Morey L, Helin K. Polycomb group protein-mediated repression of transcription. Trends Biochem Sci 2010; 35: 323-332.
37. Neff T, Sinha AU, Kluk MJ, Zhu N, Khattab MH, Stein L et al. Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc Natl Acad Sci USA 2012; 109: 5028-5033.
38. Tanaka S, Miyagi S, Sashida G, Chiba T, Yuan J, Mochizuki-Kashio M et al. Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia. Blood 2012; 120: 1107-1117.
39. Shi J, Wang E, Zuber J, Rappaport A, Taylor M, Johns C et al. The polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras( G12D) acute myeloid leukemia. Oncogene 2012; 32: 930-938.
40. Somervaille TC, Cleary ML. Grist for the MLL: how do MLL oncogenic fusion proteins generate leukemia stem cells? Int J Hematol 2010; 91: 735-741.
41. Walf-Vorderwulbecke V, de Boer J, Horton SJ, van Amerongen R, Proost N, Berns A et al. Frat2 mediates the oncogenic activation of Rac by MLL fusions. Blood 2012; 120: 4819-4828.
42. van Amerongen R, Nawijn MC, Lambooij JP, Proost N, Jonkers J, Berns A. Frat oncoproteins act at the crossroad of canonical and noncanonical Wnt-signaling pathways. Oncogene 2010; 29: 93-104.
43. Wei J, Wunderlich M, Fox C, Alvarez S, Cigudosa JC, Wilhelm JS et al. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell 2008; 13: 483-495. (Pubitemid 351763903)
44. Mizukawa B, Wei J, Shrestha M, Wunderlich M, Chou FS, Griesinger A et al. Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia. Blood 2011; 118: 5235-5245.
45. Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z et al. The Wnt/betacatenin pathway is required for the development of leukemia stem cells in AML. Science 2010; 327: 1650-1653.
46. Yeung J, Esposito MT, Gandillet A, Zeisig BB, Griessinger E, Bonnet D et al. Betacatenin mediates the establishment and drug resistance of MLL leukemic stem cells. Cancer Cell 2010; 18: 606-618.
47. Wang Z, Smith KS, Murphy M, Piloto O, Somervaille TC, Cleary ML. Glycogen synthase kinase 3 in MLL leukemia maintenance and targeted therapy. Nature 2008; 455: 1205-1209.
48. Osaki H, Walf-Vorderwulbecke V, Mangolini M, Zhao L, Horton SJ, Morrone G et al. The AAA() ATPase RUVBL2 is a critical mediator of MLL-AF9 oncogenesis. Leukemia 2013; e-pub ahead of print 13 February 2013; doi:10.1038/leu.2012.42.
49. Grigoletto A, Lestienne P, Rosenbaum J. The multifaceted proteins reptin and pontin as major players in cancer. Biochim Biophys Acta 2011; 1815: 147-157.
50. Wilkinson AC, Ballabio E, Geng H, North P, Tapia M, Kerry J et al. RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Cell Rep 2013; 3: 116-127.
51. Bursen A, Schwabe K, Ruster B, Henschler R, Ruthardt M, Dingermann T et al. The AF4.MLL fusion protein is capable of inducing ALL in mice without requirement of MLL.AF4. Blood 2010; 115: 3570-3579.
52. Emerenciano M, Kowarz E, Karl K, de Almeida Lopes B, Scholz B, Bracharz S et al. Functional analysis of the two reciprocal fusion genes MLL-NEBL and NEBL-MLL reveal their oncogenic potential. Cancer Lett 2013; 332: 30-34.
53. Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, van Putten WL, Valk PJ, van der Poel-van de Luytgaarde S, Hack R et al. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood 2003; 101: 837-845. (Pubitemid 36139348)
54. Groschel S, Lugthart S, Schlenk RF, Valk PJ, Eiwen K, Goudswaard C et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol 2010; 28: 2101-2107.
55. Groschel S, Schlenk RF, Engelmann J, Rockova V, Teleanu V, Kuhn MW et al. Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol 2013; 31: 95-103.
56. Bindels EM, Havermans M, Lugthart S, Erpelinck C, Wocjtowicz E, Krivtsov AV et al. EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs. Blood 2012; 119: 5838-5849.
57. Arai S, Yoshimi A, Shimabe M, Ichikawa M, Nakagawa M, Imai Y et al. Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells. Blood 2011; 117: 6304-6314.
58. Krivtsov AV, Figueroa ME, Sinha AU, Stubbs MC, Feng Z, Valk PJ et al. Cell of origin determines clinically relevant subtypes of MLL-rearranged AML. Leukemia 2012; e-pub ahead of print 13 December 2012; doi:10.1038/leu.2012.363.
59. Horton SJ, Jaques J, Woolthuis C, van Dijk J, Mesuraca M, Huls G et al. MLL-AF9-mediated immortalization of human hematopoietic cells along different lineages changes during ontogeny. Leukemia 2012; e-pub ahead of print 26 November 2012; doi:10.1038/leu.2012.343.
60. Chen J, Odenike O, Rowley JD. Leukaemogenesis: more than mutant genes. Nat Rev Cancer 2010; 10: 23-36.
61. Marcucci G, Mrozek K, Radmacher MD, Garzon R, Bloomfield CD. The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood 2011; 117: 1121-1129.
62. Schotte D, De Menezes RX, Akbari Moqadam F, Khankahdani LM, Lange-Turenhout E, Chen C et al. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia. Haematologica 2011; 96: 703-711.
63. Li Z, Huang H, Chen P, He M, Li Y, Arnovitz S et al. miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumor suppressor in MLL-rearranged leukaemia. Nat Commun 2012; 3: 688.
64. Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ et al. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood 2009; 113: 3314-3322.
65. Nishi M, Eguchi-Ishimae M, Wu Z, Gao W, Iwabuki H, Kawakami S et al. Suppression of the let-7b microRNA pathway by DNA hypermethylation in infant acute lymphoblastic leukemia with MLL gene rearrangements. Leukemia 2012; 27: 389-397.
66. Jiang X, Huang H, Li Z, He C, Li Y, Chen P et al. MiR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia. Proc Natl Acad Sci USA 2012; 109: 19397-19402.
67. Jiang X, Huang H, Li Z, Li Y, Wang X, Gurbuxani S et al. Blockade of miR-150 maturation by MLL-fusion/MYC/LIN-28 is required for MLL-associated leukemia. Cancer Cell 2012; 22: 524-535.
68. Bergerson RJ, Collier LS, Sarver AL, Been RA, Lugthart S, Diers MD et al. An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model. Blood 2012; 119: 4512-4523.
69. Takacova S, Slany R, Bartkova J, Stranecky V, Dolezel P, Luzna P et al. DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo. Cancer Cell 2012; 21: 517-531.
70. Zeisig BB, Milne T, Garcia-Cuellar MP, Schreiner S, Martin ME, Fuchs U et al. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol 2004; 24: 617-628. (Pubitemid 38057914)
71. Jenkins CR, Shevchuk OO, Giambra V, Lam SH, Carboni JM, Gottardis MM et al. IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein. Exp Hematol 2012; 40: 715-723e716.
72. Zorko NA, Bernot KM, Whitman SP, Siebenaler RF, Ahmed EH, Marcucci GG et al. Mll partial tandem duplication and Flt3 internal tandem duplication in a double knock-in mouse recapitulates features of counterpart human acute myeloid leukemias. Blood 2012; 120: 1130-1136.
73. Spijkers-Hagelstein JA, Schneider P, Hulleman E, de Boer J, Williams O, Pieters R et al. Elevated S100A8/S100A9 expression causes glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia. Leukemia 2012; 26: 1255-1265.
74. Spijkers-Hagelstein JA, Mimoso Pinhancos S, Schneider P, Pieters R, Stam RW. Src kinase-induced phosphorylation of annexin A2 mediates glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia. Leukemia 2012; e-pub ahead of print 28 December 2012; doi:10.1038/leu.2012.372.
75. Accordi B, Galla L, Milani G, Curtarello M, Serafin V, Lissandron V et al. AMPK inhibition enhances apoptosis in MLL-rearranged pediatric B-acute lymphoblastic leukemia cells. Leukemia 2012; e-pub ahead of print 21 November 2012; doi:10.1038/leu.2012.338.
76. Grembecka J, He S, Shi A, Purohit T, Muntean AG, Sorenson RJ et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat Chem Biol 2012; 8: 277-284.
77. Shi A, Murai MJ, He S, Lund G, Hartley T, Purohit T et al. Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia. Blood 2012; 120: 4461-4469.
78. Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011; 20: 53-65.
79. Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A et al. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun 2012; 3: 1288.
80. Sukhai MA, Spagnuolo PA, Weir S, Kasper J, Patton L, Schimmer AD. New sources of drugs for hematologic malignancies. Blood 2011; 117: 6747-6755.
81. Lamb J. The Connectivity Map: a new tool for biomedical research. Nat Rev Cancer 2007; 7: 54-60. (Pubitemid 46020847)
82. Stumpel DJ, Schneider P, Seslija L, Osaki H, Williams O, Pieters R et al. Connectivity mapping identifies HDAC inhibitors for the treatment of t(4;11)-positive infant acute lymphoblastic leukemia. Leukemia 2012; 26: 682-692.