Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Molecular genetics of acute myeloid leukemia

Wendy Stock, MD
Michael J Thirman, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


Acute myeloid leukemia (AML) develops as the consequence of a series of genetic changes in a hematopoietic precursor cell. These changes alter normal hematopoietic growth and differentiation, resulting in an accumulation of large numbers of abnormal, immature myeloid cells in the bone marrow and peripheral blood. These cells are capable of dividing and proliferating, but cannot differentiate into mature hematopoietic cells (ie, neutrophils).

Similar to other malignancies, the genetic alterations in AML include mutation of oncogenes as well as the loss of tumor suppressor genes. In contrast to most solid tumors, many hematologic malignancies are associated with a single characteristic cytogenetic abnormality (eg, the Philadelphia chromosome [t(9;22)] in chronic myeloid leukemia and t(15;17) in acute promyelocytic leukemia).

Advances in the identification of recurring chromosomal abnormalities and translocations have provided major insight into the pathobiology of AML. (See "Tools for genetics and genomics: Cytogenetics and molecular genetics".)

Specific cytogenetic abnormalities identified by karyotype analysis have considerable prognostic significance for patients with AML and affect treatment planning. Abnormalities in certain genes (eg, mutations in FLT3, nucleophosmin, KIT) as well as gene expression profiles confer prognostic significance in adult patients with AML. Even those patients without obvious abnormalities detected by karyotypic analysis or gene expression profiles have acquired copy number alterations that may help to identify genes important for the pathogenesis of AML [1,2]. (See "Prognosis of acute myeloid leukemia".)

The focus of this topic review will be on the various molecular genetic events involved in the pathogenesis of AML. More general discussions of genetic events in hematologic malignancies are presented separately. (See "Genetic abnormalities in hematologic and lymphoid malignancies" and "General aspects of cytogenetic analysis in hematologic malignancies".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Mar 2, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Walter MJ, Payton JE, Ries RE, et al. Acquired copy number alterations in adult acute myeloid leukemia genomes. Proc Natl Acad Sci U S A 2009; 106:12950.
  2. Radtke I, Mullighan CG, Ishii M, et al. Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia. Proc Natl Acad Sci U S A 2009; 106:12944.
  3. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013; 368:2059.
  4. Marcucci G, Yan P, Maharry K, et al. Epigenetics meets genetics in acute myeloid leukemia: clinical impact of a novel seven-gene score. J Clin Oncol 2014; 32:548.
  5. Cheung N, Fung TK, Zeisig BB, et al. Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia. Cancer Cell 2016; 29:32.
  6. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010; 363:2424.
  7. Yan XJ, Xu J, Gu ZH, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011; 43:309.
  8. Ito S, D'Alessio AC, Taranova OV, et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010; 466:1129.
  9. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009; 360:2289.
  10. Li Z, Cai X, Cai CL, et al. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood 2011; 118:4509.
  11. Ahuja H, Bar-Eli M, Arlin Z, et al. The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia. J Clin Invest 1991; 87:2042.
  12. Kelman Z, Prokocimer M, Peller S, et al. Rearrangements in the p53 gene in Philadelphia chromosome positive chronic myelogenous leukemia. Blood 1989; 74:2318.
  13. Mashal R, Shtalrid M, Talpaz M, et al. Rearrangement and expression of p53 in the chronic phase and blast crisis of chronic myelogenous leukemia. Blood 1990; 75:180.
  14. Mori N, Hidai H, Yokota J, et al. Mutations of the p53 gene in myelodysplastic syndrome and overt leukemia. Leuk Res 1995; 19:869.
  15. Lanza C, Gaidano G, Cimino G, et al. p53 gene inactivation in acute lymphoblastic leukemia of B cell lineage associates with chromosomal breakpoints at 11q23 and 8q24. Leukemia 1995; 9:955.
  16. Lanza C, Gaidano G, Cimino G, et al. Distribution of TP53 mutations among acute leukemias with MLL rearrangements. Genes Chromosomes Cancer 1996; 15:48.
  17. Rücker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood 2012; 119:2114.
  18. Inoue K, Sugiyama H, Ogawa H, et al. WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. Blood 1994; 84:3071.
  19. Bergmann L, Miething C, Maurer U, et al. High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood 1997; 90:1217.
  20. Call KM, Glaser T, Ito CY, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 1990; 60:509.
  21. Haber DA, Buckler AJ, Glaser T, et al. An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell 1990; 61:1257.
  22. Baird PN, Simmons PJ. Expression of the Wilms' tumor gene (WT1) in normal hemopoiesis. Exp Hematol 1997; 25:312.
  23. Stiller CA, Chessells JM, Fitchett M. Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study. Br J Cancer 1994; 70:969.
  24. Shannon KM, O'Connell P, Martin GA, et al. Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. N Engl J Med 1994; 330:597.
  25. Hirama T, Koeffler HP. Role of the cyclin-dependent kinase inhibitors in the development of cancer. Blood 1995; 86:841.
  26. Campos L, Rouault JP, Sabido O, et al. High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood 1993; 81:3091.
  27. Le Beau MM, Albain KS, Larson RA, et al. Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7. J Clin Oncol 1986; 4:325.
  28. Pedersen-Bjergaard J, Philip P. Two different classes of therapy-related and de-novo acute myeloid leukemia? Cancer Genet Cytogenet 1991; 55:119.
  29. Thirman MJ, Larson RA. Therapy-related myeloid leukemia. Hematol Oncol Clin North Am 1996; 10:293.
  30. Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 2001; 97:2434.
  31. Bacher U, Haferlach C, Kern W, et al. Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients. Blood 2008; 111:2527.
  32. Zeleznik-Le NJ, Nucifora G, Rowley JD. The molecular biology of myeloproliferative disorders as revealed by chromosomal abnormalities. Semin Hematol 1995; 32:201.
  33. Ahuja HG, Foti A, Bar-Eli M, Cline MJ. The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing. Blood 1990; 75:1684.
  34. Neubauer A, Dodge RK, George SL, et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood 1994; 83:1603.
  35. Bartram CR. Molecular genetic aspects of myelodysplastic syndromes. Hematol Oncol Clin North Am 1992; 6:557.
  36. Nakagawa T, Saitoh S, Imoto S, et al. Multiple point mutation of N-ras and K-ras oncogenes in myelodysplastic syndrome and acute myelogenous leukemia. Oncology 1992; 49:114.
  37. Bos JL. ras oncogenes in human cancer: a review. Cancer Res 1989; 49:4682.
  38. Taylor JA, Sandler DP, Bloomfield CD, et al. ras oncogene activation and occupational exposures in acute myeloid leukemia. J Natl Cancer Inst 1992; 84:1626.
  39. Lübbert M, Mirro J Jr, Kitchingman G, et al. Prevalence of N-ras mutations in children with myelodysplastic syndromes and acute myeloid leukemia. Oncogene 1992; 7:263.
  40. Paquette RL, Landaw EM, Pierre RV, et al. N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome. Blood 1993; 82:590.
  41. Liu ET, Dodge R, Myer A, et al. De novo acute myeloid leukemias harboring ras mutations exhibit preferential sensitivity to dose intensive cytarabine as consolidation therapy. Blood 1995; 86:598a.
  42. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005; 352:254.
  43. Rabbitts TH. Chromosomal translocations in human cancer. Nature 1994; 372:143.
  44. Tenen DG, Hromas R, Licht JD, Zhang DE. Transcription factors, normal myeloid development, and leukemia. Blood 1997; 90:489.
  45. Sawyers CL. Molecular genetics of acute leukaemia. Lancet 1997; 349:196.
  46. Shivdasani RA, Orkin SH. The transcriptional control of hematopoiesis. Blood 1996; 87:4025.
  47. Alcalay M, Meani N, Gelmetti V, et al. Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair. J Clin Invest 2003; 112:1751.
  48. Nichols J, Nimer SD. Transcription factors, translocations, and leukemia. Blood 1992; 80:2953.
  49. Wang Q, Stacy T, Miller JD, et al. The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell 1996; 87:697.
  50. Marcucci G, Caligiuri MA, Bloomfield CD. Molecular and clinical advances in core binding factor primary acute myeloid leukemia: a paradigm for translational research in malignant hematology. Cancer Invest 2000; 18:768.
  51. Rodan GA, Harada S. The missing bone. Cell 1997; 89:677.
  52. Michaud J, Scott HS, Escher R. AML1 interconnected pathways of leukemogenesis. Cancer Invest 2003; 21:105.
  53. Wang S, Wang Q, Crute BE, et al. Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. Mol Cell Biol 1993; 13:3324.
  54. Tanaka T, Tanaka K, Ogawa S, et al. An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms. EMBO J 1995; 14:341.
  55. Okuda T, van Deursen J, Hiebert SW, et al. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 1996; 84:321.
  56. Sasaki K, Yagi H, Bronson RT, et al. Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta. Proc Natl Acad Sci U S A 1996; 93:12359.
  57. Harada H, Harada Y, Tanaka H, et al. Implications of somatic mutations in the AML1 gene in radiation-associated and therapy-related myelodysplastic syndrome/acute myeloid leukemia. Blood 2003; 101:673.
  58. Nakao M, Horiike S, Fukushima-Nakase Y, et al. Novel loss-of-function mutations of the haematopoiesis-related transcription factor, acute myeloid leukaemia 1/runt-related transcription factor 1, detected in acute myeloblastic leukaemia and myelodysplastic syndrome. Br J Haematol 2004; 125:709.
  59. Chen CY, Lin LI, Tang JL, et al. RUNX1 gene mutation in primary myelodysplastic syndrome--the mutation can be detected early at diagnosis or acquired during disease progression and is associated with poor outcome. Br J Haematol 2007; 139:405.
  60. Ding Y, Harada Y, Imagawa J, et al. AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood 2009; 114:5201.
  61. Nucifora G, Rowley JD. AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Blood 1995; 86:1.
  62. Bloomfield CD, Lawrence D, Arthur DC, et al. Curative impact of intensification with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) varies by cytogenetic group. Blood 1994; 84:111a.
  63. Nucifora G, Dickstein JI, Torbenson V, et al. Correlation between cell morphology and expression of the AML1/ETO chimeric transcript in patients with acute myeloid leukemia without the t(8;21). Leukemia 1994; 8:1533.
  64. Erickson P, Gao J, Chang KS, et al. Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood 1992; 80:1825.
  65. Linggi B, Müller-Tidow C, van de Locht L, et al. The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nat Med 2002; 8:743.
  66. Vangala RK, Heiss-Neumann MS, Rangatia JS, et al. The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia. Blood 2003; 101:270.
  67. Rhoades KL, Hetherington CJ, Rowley JD, et al. Synergistic up-regulation of the myeloid-specific promoter for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis. Proc Natl Acad Sci U S A 1996; 93:11895.
  68. Pabst T, Mueller BU, Harakawa N, et al. AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nat Med 2001; 7:444.
  69. Yergeau DA, Hetherington CJ, Wang Q, et al. Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nat Genet 1997; 15:303.
  70. Yin CC, Cortes J, Barkoh B, et al. t(3;21)(q26;q22) in myeloid leukemia: an aggressive syndrome of blast transformation associated with hydroxyurea or antimetabolite therapy. Cancer 2006; 106:1730.
  71. Nucifora G, Birn DJ, Espinosa R 3rd, et al. Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis. Blood 1993; 81:2728.
  72. Mitani K, Ogawa S, Tanaka T, et al. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J 1994; 13:504.
  73. Suzukawa K, Parganas E, Gajjar A, et al. Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI1 gene in acute myelogenous leukemias with inv(3)(q21q26). Blood 1994; 84:2681.
  74. Zent CS, Mathieu C, Claxton DF, et al. The chimeric genes AML1/MDS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties. Proc Natl Acad Sci U S A 1996; 93:1044.
  75. Golub TR, Barker GF, Bohlander SK, et al. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 1995; 92:4917.
  76. Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 1994; 77:307.
  77. Golub TR, Goga A, Barker GF, et al. Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia. Mol Cell Biol 1996; 16:4107.
  78. Bloomfield CD, Lawrence D, Byrd JC, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 1998; 58:4173.
  79. Liu P, Tarlé SA, Hajra A, et al. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science 1993; 261:1041.
  80. Castilla LH, Wijmenga C, Wang Q, et al. Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Cell 1996; 87:687.
  81. Thirman MJ, Gill HJ, Burnett RC, et al. Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 1993; 329:909.
  82. Schoch C, Schnittger S, Klaus M, et al. AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood 2003; 102:2395.
  83. Basecke J, Whelan JT, Griesinger F, Bertrand FE. The MLL partial tandem duplication in acute myeloid leukaemia. Br J Haematol 2006; 135:438.
  84. Kaltenbach S, Soler G, Barin C, et al. NUP98-MLL fusion in human acute myeloblastic leukemia. Blood 2010; 116:2332.
  85. Meyer C, Hofmann J, Burmeister T, et al. The MLL recombinome of acute leukemias in 2013. Leukemia 2013; 27:2165.
  86. Blum W, Mrózek K, Ruppert AS, et al. Adult de novo acute myeloid leukemia with t(6;11)(q27;q23): results from Cancer and Leukemia Group B Study 8461 and review of the literature. Cancer 2004; 101:1420.
  87. Jourdan E, Dastugue N. Adult de novo acute myeloid leukemia with t(6;11)(q27;q23): results from Cancer and Leukemia Group B Study 8461 and review of the literature. Cancer 2005; 103:1316; author reply 1316.
  88. Schichman SA, Canaani E, Croce CM. Self-fusion of the ALL1 gene. A new genetic mechanism for acute leukemia. JAMA 1995; 273:571.
  89. Caligiuri MA, Strout MP, Schichman SA, et al. Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11. Cancer Res 1996; 56:1418.
  90. Ziemin-van der Poel S, McCabe NR, Gill HJ, et al. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A 1991; 88:10735.
  91. Gu Y, Nakamura T, Alder H, 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.
  92. Tkachuk DC, Kohler S, Cleary ML. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell 1992; 71:691.
  93. Djabali M, Selleri L, Parry P, et al. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet 1993; 4:431.
  94. Mazo AM, Huang DH, Mozer BA, Dawid IB. The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains. Proc Natl Acad Sci U S A 1990; 87:2112.
  95. Liedtke M, Cleary ML. Therapeutic targeting of MLL. Blood 2009; 113:6061.
  96. Milne TA, Kim J, Wang GG, et al. Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol Cell 2010; 38:853.
  97. Wang Z, Song J, Milne TA, et al. Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. Cell 2010; 141:1183.
  98. Muntean AG, Tan J, Sitwala K, et al. The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. Cancer Cell 2010; 17:609.
  99. Wang Z, Iwasaki M, Ficara F, et al. GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis. Cancer Cell 2010; 17:597.
  100. Jin S, Zhao H, Yi Y, et al. c-Myb binds MLL through menin in human leukemia cells and is an important driver of MLL-associated leukemogenesis. J Clin Invest 2010; 120:593.
  101. Mohan M, Lin C, Guest E, Shilatifard A. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat Rev Cancer 2010; 10:721.
  102. Lin C, Smith ER, Takahashi H, 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.
  103. Corral J, Lavenir I, Impey H, 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.
  104. 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.
  105. Lavau C, Luo RT, Du C, Thirman MJ. Retrovirus-mediated gene transfer of MLL-ELL transforms primary myeloid progenitors and causes acute myeloid leukemias in mice. Proc Natl Acad Sci U S A 2000; 97:10984.
  106. Luo RT, Lavau C, Du C, et al. The elongation domain of ELL is dispensable but its ELL-associated factor 1 interaction domain is essential for MLL-ELL-induced leukemogenesis. Mol Cell Biol 2001; 21:5678.
  107. DiMartino JF, Miller T, Ayton PM, et al. A carboxy-terminal domain of ELL is required and sufficient for immortalization of myeloid progenitors by MLL-ELL. Blood 2000; 96:3887.
  108. de Thé H, Chomienne C, Lanotte M, et al. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature 1990; 347:558.
  109. von Lindern M, Breems D, van Baal S, et al. Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia. Genes Chromosomes Cancer 1992; 5:227.
  110. Ichikawa H, Shimizu K, Hayashi Y, Ohki M. An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res 1994; 54:2865.
  111. Panagopoulos I, Aman P, Fioretos T, et al. Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Genes Chromosomes Cancer 1994; 11:256.
  112. Rabbitts TH, Forster A, Larson R, Nathan P. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet 1993; 4:175.
  113. Sorensen PH, Lessnick SL, Lopez-Terrada D, et al. A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet 1994; 6:146.
  114. Panagopoulos I, Höglund M, Mertens F, et al. Fusion of the EWS and CHOP genes in myxoid liposarcoma. Oncogene 1996; 12:489.
  115. Yoneda-Kato N, Look AT, Kirstein MN, et al. The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. Oncogene 1996; 12:265.
  116. Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994; 263:1281.
  117. Lugthart S, Gröschel S, Beverloo HB, et al. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol 2010; 28:3890.
  118. Hui CH, Suttle J. Erythrophagocytosis associated with AML-M5 and t(8;16). Br J Haematol 2001; 113:845.
  119. Sobulo OM, Borrow J, Tomek R, et al. MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). Proc Natl Acad Sci U S A 1997; 94:8732.
  120. Caudell D, Aplan PD. The role of CALM-AF10 gene fusion in acute leukemia. Leukemia 2008; 22:678.
  121. Borrow J, Shearman AM, Stanton VP Jr, et al. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet 1996; 12:159.
  122. Jankovic D, Gorello P, Liu T, et al. Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia. Blood 2008; 111:5672.
  123. Metz T, Graf T. Fusion of the nuclear oncoproteins v-Myb and v-Ets is required for the leukemogenicity of E26 virus. Cell 1991; 66:95.
  124. Graf T, McNagny K, Brady G, Frampton J. Chicken "erythroid" cells transformed by the Gag-Myb-Ets-encoding E26 leukemia virus are multipotent. Cell 1992; 70:201.
  125. Mucenski ML, McLain K, Kier AB, et al. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell 1991; 65:677.
  126. Nazarov V, Hilbert D, Wolff L. Susceptibility and resistance to Moloney murine leukemia virus-induced promonocytic leukemia. Virology 1994; 205:479.
  127. Nazarov V, Wolff L. Novel integration sites at the distal 3' end of the c-myb locus in retrovirus-induced promonocytic leukemias. J Virol 1995; 69:3885.
  128. Ben-David Y, Bernstein A. Friend virus-induced erythroleukemia and the multistage nature of cancer. Cell 1991; 66:831.
  129. Munroe DG, Peacock JW, Benchimol S. Inactivation of the cellular p53 gene is a common feature of Friend virus-induced erythroleukemia: relationship of inactivation to dominant transforming alleles. Mol Cell Biol 1990; 10:3307.
  130. Lavigueur A, Bernstein A. p53 transgenic mice: accelerated erythroleukemia induction by Friend virus. Oncogene 1991; 6:2197.
  131. Moreau-Gachelin F, Ray D, Mattei MG, et al. The putative oncogene Spi-1: murine chromosomal localization and transcriptional activation in murine acute erythroleukemias. Oncogene 1989; 4:1449.
  132. Paul R, Schuetze S, Kozak SL, et al. The Sfpi-1 proviral integration site of Friend erythroleukemia encodes the ets-related transcription factor Pu.1. J Virol 1991; 65:464.
  133. Scott EW, Simon MC, Anastasi J, Singh H. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 1994; 265:1573.
  134. Buchberg AM, Bedigian HG, Jenkins NA, Copeland NG. Evi-2, a common integration site involved in murine myeloid leukemogenesis. Mol Cell Biol 1990; 10:4658.
  135. Largaespada DA, Shaughnessy JD Jr, Jenkins NA, Copeland NG. Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels. J Virol 1995; 69:5095.
  136. Cho BC, Shaughnessy JD Jr, Largaespada DA, et al. Frequent disruption of the Nf1 gene by a novel murine AIDS virus-related provirus in BXH-2 murine myeloid lymphomas. J Virol 1995; 69:7138.
  137. Shannon KM, Watterson J, Johnson P, et al. Monosomy 7 myeloproliferative disease in children with neurofibromatosis, type 1: epidemiology and molecular analysis. Blood 1992; 79:1311.
  138. Jacks T, Shih TS, Schmitt EM, et al. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet 1994; 7:353.
  139. Bollag G, Clapp DW, Shih S, et al. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet 1996; 12:144.
  140. Largaespada DA, Brannan CI, Jenkins NA, Copeland NG. Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nat Genet 1996; 12:137.
  141. Nakamura T, Largaespada DA, Shaughnessy JD Jr, et al. Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias. Nat Genet 1996; 12:149.
  142. Nakamura T, Jenkins NA, Copeland NG. Identification of a new family of Pbx-related homeobox genes. Oncogene 1996; 13:2235.
  143. Vassiliou GS, Cooper JL, Rad R, et al. Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat Genet 2011; 43:470.