Classification of mixed-lineage leukemia fusion partners predicts additional cancer pathways

Annals of Laboratory Medicine

Volumn 36, Issue 2, 2016, Pages 85-100

  Marschalek, Rolf ^a  

^a GOETHE UNIVERSITY   (Germany)

Author keywords

MLL r leukemia; Molecular mechanisms of cancer; Translocation partner genes

Indexed keywords

MIXED LINEAGE LEUKEMIA PROTEIN;

ALLELE; CHEMISTRY; CLASSIFICATION; GENE TRANSLOCATION; GENETIC EPIGENESIS; GENETICS; HUMAN; LEUKEMIA; PATHOLOGY; PROTEIN TERTIARY STRUCTURE; X CHROMOSOME;

ALLELES; CHROMOSOMES, HUMAN, X; EPIGENESIS, GENETIC; HUMANS; LEUKEMIA; MYELOID-LYMPHOID LEUKEMIA PROTEIN; PROTEIN STRUCTURE, TERTIARY; TRANSLOCATION, GENETIC;

EID: 84952929232     PISSN: 22343806     EISSN: 22343814     Source Type: Journal    
DOI: 10.3343/alm.2016.36.2.85     Document Type: Review

References (100)

1. Nilson I, Löchner K, Siegler G, Greil J, Beck JD, Fey GH, et al. Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias. Br J Haematol 1996;93:966-72.
2. Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa R 3rd, 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;88:10735-9.
3. Corral J, Lavenir I, Impey H, Warren AJ, Forster A, Larson TA, et al. An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: A method to create fusion oncogenes. Cell 1996;85:853-61.
4. Lavau C, Szilvassy SJ, Slany R, Cleary ML. Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. EMBO J 1997;16:4226-37.
5. DiMartino JF, Miller T, Ayton PM, Landewe T, Hess JL, Cleary ML, et al. A carboxy-terminal domain of ELL is required and sufficient for immortalization of myeloid progenitors by MLL-ELL. Blood 2000;96:3887-93.
6. DiMartino JF, Ayton PM, Chen EH, Naftzger CC, Young BD, Cleary ML. The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10. Blood 2002;99:3780-5.
7. So CW, Karsunky H, Wong P, Weissman IL, Cleary ML. Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. Blood 2004;103:3192-9.
8. 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;14:355-68.
9. Bursen A, Schwabe K, Rüster 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;115:3570-9.
10. Greaves M. When one mutation is all it takes. Cancer Cell 2015;27:433-4.
11. Jude CD, Climer L, Xu D, Artinger E, Fisher JK, Ernst P. Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors. Cell Stem Cell 2007;1:324-37.
12. 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;117:6304-14.
13. Huang X, Spencer GJ, Lynch JT, Ciceri F, Somerville TD, Somervaille TC. Enhancers of Polycomb EPC1 and EPC2 sustain the oncogenic potential of MLL leukemia stem cells. Leukemia 2014;28:1081-91.
14. Zhou J, Wu J, Li B, Liu D, Yu J, Yan X, et al. PU.1 is essential for MLL leukemia partially via crosstalk with the MEIS/HOX pathway. Leukemia 2014;28:1436-48.
15. Park SM, Gönen M, Vu L, Minuesa G, Tivnan P, Barlowe TS, et al. Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program. J Clin Invest 2015;125:1286-98.
16. Meyer C, Hofmann J, Burmeister T, Gröger D, Park TS, Emerenciano M, et al. The MLL recombinome of acute leukemias in 2013. Leukemia 2013;27:2165-76.
17. Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009;114:2489-96.
18. Ayton PM and Cleary ML. Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9. Genes Dev 2003;17: 2298-307.
19. Ernst P, Mabon M, Davidson AJ, Zon LI, Korsmeyer SJ. An Mll-dependent Hox program drives hematopoietic progenitor expansion. Curr Biol 2004;14:2063-9.
20. 1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, et al. A map of human genome variation from population-scale sequencing. Nature 2010;467:1061-73.
21. Reichel M, Gillert E, Nilson I, Siegler G, Greil J, Fey GH, et al. Fine structure of translocation breakpoints in leukemic blasts with chromosomal translocation t(4;11): The DNA damage-repair model of translocation. Oncogene 1998;17:3035-44.
22. Gillert E, Leis T, Repp R, Reichel M, Hösch A, Breitenlohner I, et al. A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells. Oncogene 1999;18: 4663-71.
23. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 2011;144:27-40.
24. Djabali M, Selleri L, Parry P, Bower M, Young BD, Evans GA. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet 1992;2:113-8.
25. 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.
26. 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; 71:701-8.
27. Rasio D, Schichman SA, Negrini M, Canaani E, Croce CM. Complete exon structure of the ALL1 gene. Cancer Res 1996;56:1766-9.
28. Meyer C, Kowarz E, Schneider B, Oehm C, Klingebiel T, Dingermann T, et al. Genomic DNA of leukemic patients: Target for clinical diagnosis of MLL rearrangements. Biotechnol J 2006;1:656-63.
29. Rössler T and Marschalek R. An alternative splice process renders the MLL protein either into a transcriptional activator or repressor. Pharmazie 2013;68:601-7.
30. Zeisig DT, Bittner CB, Zeisig BB, García-Cuéllar MP, Hess JL, Slany RK. The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin. Oncogene 2005;24:5525-32.
31. Bitoun E, Oliver PL, Davies KE. The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum Mol Genet 2007;16: 92-106.
32. Mueller D, García-Cuéllar MP, Bach C, Buhl S, Maethner E, Slany RK. Misguided transcriptional elongation causes mixed lineage leukemia. PLoS Biol 2009;7:e1000249.
33. Benedikt A, Baltruschat S, Scholz B, Bursen A, Arrey TN, Meyer B, et al. The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. Leukemia 2011;25:135-44.
34. Hsieh JJ, Cheng EH, Korsmeyer SJ. Taspase1: A threonine aspartase required for cleavage of MLL and proper HOX gene expression. Cell 2003;115:293-303.
35. Adler HT, Nallaseth FS, Walter G, Tkachuk DC. HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A. J Biol Chem 1997;272:28407-14.
36. Adler HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ Jr, et al. Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins. Mol Cell Biol 1999;19:7050-60.
37. Nakamura T, Mori T, Tada S, Krajewski W, Rozovskaia T, Wassell R, et al. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell 2002;10: 1119-28.
38. Yokoyama A, Kitabayashi I, Ayton PM, Cleary ML, Ohki M. Leukemia proto-oncoprotein MLL is proteolytically processed into 2 fragments with opposite transcriptional properties. Blood 2002;100:3710-8.
39. Xia ZB, Anderson M, Diaz MO, Zeleznik-Le NJ. MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc Natl Acad Sci USA 2003;100:8342-7.
40. 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;24:5639-49.
41. Wysocka J, Swigut T, Milne TA, Dou Y, Zhang X, Burlingame AL, et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 2005;121:859-72.
42. Dou Y, Milne TA, Tackett AJ, Smith ER, Fukuda A, Wysocka J, et al. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 2005;121: 873-85.
43. Dou Y, Milne TA, Ruthenburg AJ, Lee S, Lee JW, Verdine GL, et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol 2006;13:713-9.
44. Milne TA, Kim J, Wang GG, Stadler SC, Basrur V, Whitcomb SJ, et al. Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol Cell 2010;38:853-63.
45. Muntean AG, Tan J, Sitwala K, Huang Y, Bronstein J, Connelly JA, et al. The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. Cancer Cell 2010;17:609-21.
46. Chang PY, Hom RA, Musselman CA, Zhu L, Kuo A, Gozani O, et al. Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL-dependent gene transcription. J Mol Biol 2010;400:137-44.
47. Hom RA, Chang PY, Roy S, Musselman CA, Glass KC, Selezneva AI, et al. Molecular mechanism of MLL PHD3 and RNA recognition by the Cyp33 RRM domain. J Mol Biol 2010;400:145-54.
48. Wang Z, Song J, Milne TA, Wang GG, Li H, Allis CD, et al. Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. Cell 2010;141:1183-94.
49. Schraets D, Lehmann T, Dingermann T, Marschalek R. MLL-mediated transcriptional gene regulation investigated by gene expression profiling. Oncogene 2003;22:3655-68.
50. Chen J, Santillan DA, Koonce M, Wei W, Luo R, Thirman MJ, et al. Loss of MLL PHD finger 3 is necessary for MLL-ENL-induced hematopoietic stem cell immortalization. Cancer Res 2008;68:6199-207.
51. Muntean AG, Giannola D, Udager AM, Hess JL. The PHD fingers of MLL block MLL fusion protein-mediated transformation. Blood 2008; 112:4690-3.
52. Hayette S, Tigaud I, Maguer-Satta V, Bartholin L, Thomas X, Charrin C, et al. Recurrent involvement of the MLL gene in adult T-lineage acute lymphoblastic leukemia. Blood 2002;99:4647-9.
53. Quigley DI and Wolff DJ. Pediatric T-cell acute lymphoblastic leukemia with aberrations of both MLL loci. Cancer Genet Cytogenet 2006;168: 77-9.
54. Türkmen S, Timmermann B, Bartels G, Gröger D, Meyer C, Schwartz S, et al. Involvement of the MLL gene in adult T-lymphoblastic leukemia. Genes Chromosomes Cancer 2012;51:1114-24.
55. Broeker PL, Super HG, Thirman MJ, Pomykala H, Yonebayashi Y, Tanabe S, et al. Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites. Blood 1996;87:1912-22.
56. Cimino G, Rapanotti MC, Biondi A, Elia L, Lo Coco F, Price C, et al. Infant acute leukemias show the same biased distribution of ALL1 gene breaks as topoisomerase II related secondary acute leukemias. Cancer Res 1997;57:2879-83.
57. Felix CA, Hosler MR, Slater DJ, Parker RI, Masterson M, Whitlock JA, et al. MLL genomic breakpoint distribution within the breakpoint cluster region in de novo leukemia in children. J Pediatr Hematol Oncol 1998; 20:299-308.
58. Reichel M, Gillert E, Angermüller S, Hensel JP, Heidel F, Lode M, et al. Biased distribution of chromosomal breakpoints involving the MLL gene in infants versus children and adults with t(4;11) ALL. Oncogene 2001; 20:2900-7.
59. Wang J, Muntean AG, Hess JL. ECSASB2 mediates MLL degradation during hematopoietic differentiation. Blood 2012;119:1151-61.
60. Marschalek R. It takes two-to-leukemia: About addictions and requirements. Leuk Res 2011;35:424-5.
61. Emerenciano M, Meyer C, Mansur MB, Marschalek R, Pombo-de-Oliveira MS; Brazilian Collaborative Study Group of Infant Acute Leukaemia. The distribution of MLL breakpoints correlates with outcome in infant acute leukaemia. Br J Haematol 2013;161:224-36.
62. Scholz B, Kowarz E, Rössler T, Ahmad K, Steinhilber D, Marschalek R. AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions. Am J Blood Res 2015;5:10-24.
63. Gaussmann A, Wenger T, Eberle I, Bursen A, Bracharz S, Herr I, et al. Combined effects of the two reciprocal t(4;11) fusion proteins MLL-AF4 and AF4-MLL confer resistance to apoptosis, cell cycling capacity and growth transformation. Oncogene 2007;26:3352-63.
64. Eberle I, Pless B, Braun M, Dingermann T, Marschalek R. Transcriptional properties of human NANOG1 and NANOG2 in acute leukemic cells. Nucleic Acids Res 2010;38:5384-95.
65. Takahashi K and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663-76.
66. Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev 2011;25:661-72.
67. Luo Z, Lin C, Shilatifard A. The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol 2012;13:543-7.
68. Zheng X, Güller S, Beissert T, Puccetti E, Ruthardt M. BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility. BMC Cancer 2006; 6:262.
69. Zheng X, Oancea C, Henschler R, Moore MA, Ruthardt M. Reciprocal t(9;22) ABL/BCR fusion proteins: leukemogenic potential and effects on B cell commitment. PLoS One 2009;4:e7661.
70. Rafiei A, Mian AA, Döring C, Metodieva A, Oancea C, Thalheimer FB, et al. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome-positive acute lymphatic leukemia. PLoS Genet 2015;11:e1005144.
71. Essers MA and Trumpp A. Targeting leukemic stem cells by breaking their dormancy. Mol Oncol 2010;4:443-50.
72. Walf-Vorderwülbecke 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;120:4819-28.
73. Wang Z, Smith KS, Murphy M, Piloto O, Somervaille TC, Cleary ML. Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy. Nature 2008;455:1205-9.
74. Maucuer A, Camonis JH, Sobel A. Stathmin interaction with a putative kinase and coiled-coil-forming protein domains. Proc Natl Acad Sci USA 1995;92:3100-4.
75. Jackson BC, Ivanova IA, Dagnino L. An ELMO2-RhoG-ILK network modulates microtubule dynamics. Mol Biol Cell 2015;26:2712-25.
76. Cassimeris L. The oncoprotein 18/stathmin family of microtubule destabilizers. Curr Opin Cell Biol 2002;14:18-24.
77. Holmfeldt P, Sellin ME, Gullberg M. Upregulated Op18/stathmin activity causes chromosomal instability through a mechanism that evades the spindle assembly checkpoint. Exp Cell Res 2010;316:2017-26.
78. Machado-Neto JA, Saad ST, Traina F. Stathmin 1 in normal and malignant hematopoiesis. BMB Rep 2014;47:660-5.
79. Slagsvold T, Pattni K, Malerød L, Stenmark H. Endosomal and non-endosomal functions of ESCRT proteins. Trends Cell Biol 2006;16:317-26.
80. Webber J, Yeung V, Clayton A. Extracellular vesicles as modulators of the cancer microenvironment. Semin Cell Dev Biol 2015;40:27-34.
81. Boyiadzis M and Whiteside TL. Information transfer by exosomes: A new frontier in hematologic malignancies. Blood Rev 2015;29:281-90.
82. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics 2010;73:1907-20.
83. Prokopi M, Kousparou CA, Epenetos AA. The secret role of microRNAs in cancer stem cell development and potential therapy: A Notch-pathway approach. Front Oncol 2015;4:389.
84. Shilatifard A. Identification and purification of the Holo-ELL complex. Evidence for the presence of ELL-associated proteins that suppress the transcriptional inhibitory activity of ELL. J Biol Chem 1998;273:11212-7.
85. Kamura T, Burian D, Khalili H, Schmidt SL, Sato S, Liu WJ, et al. Cloning and characterization of ELL-associated proteins EAP45 and EAP20. a role for yeast EAP-like proteins in regulation of gene expression by glucose. J Biol Chem 2001;276:16528-33.
86. Kushwah R, Guezguez B, Lee JB, Hopkins CI, Bhatia M. Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human. EMBO Rep 2014;15:1128-38.
87. Gao X and Hardwidge PR. Ribosomal protein s3: A multifunctional target of attaching/effacing bacterial pathogens. Front Microbiol 2011;2: 137.
88. Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 2013;122:1017-25.
89. Borkin D, He S, Miao H, Kempinska K, Pollock J, Chase J, et al. Pharmacologic iInhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell 2015;27:589-602.
90. Jones WD, Dafou D, McEntagart M, Woollard WJ, Elmslie FV, Holder-Espinasse M, et al. De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet 2012;91:358-64.
91. Ahmad K, Katryniok C, Scholz B, Merkens J, Löscher D, Marschalek R, et al. Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wild-type MLL. Oncogenesis 2014;3:e127.
92. Bursen A, Moritz S, Gaussmann A, Moritz S, Dingermann T, Marschalek R. Interaction of AF4 wild-type and AF4.MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology? Oncogene 2004;23:6237-49.
93. Kumar AR, Yao Q, Li Q, Sam TA, Kersey JH. T(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. Leuk Res 2011;35:305-9.
94. Sanders DS, Muntean AG, Hess JL. Significance of AF4-MLL reciprocal fusion in t(4;11) leukemias? Leuk Res 2011;35:299-300.
95. 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;332:30-4.
96. 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;3:116-27.
97. Wächter K, Kowarz E, Marschalek R. Functional characterisation of different MLL fusion proteins by using inducible Sleeping Beauty vectors. Cancer Lett 2014;352:196-202.
98. Breese EH, Buechele C, Dawson C, Cleary ML, Porteus MH. Use of genome engineering to create patient specific MLL translocations in primary human hematopoietic stem and progenitor cells. PLoS ONE 2015; 10:e0136644.
99. Sabiani S, Geppert T, Engelbrecht C, Kowarz E, Schneider G, Marschalek R. Unraveling the activation mechanism of Taspase1 which controls the oncogenic AF4-MLL fusion protein. EBio Medicine 2015;2:386-95.
100. Cao F, Townsend EC, Karatas H, Xu J, Li L, Lee S, et al. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol Cell 2014;53:247-61.