Molecular genetics of acute lymphoblastic leukemia

Journal of Clinical Oncology

Volumn 23, Issue 26, 2005, Pages 6306-6315

  Armstrong, Scott A ^a   Look, A Thomas ^a  

^a BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; IMATINIB; JANUS KINASE 2; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN TYROSINE KINASE INHIBITOR; TRANSCRIPTION FACTOR ETV6; TRANSCRIPTION FACTOR RUNX1; ONCOPROTEIN;

ACUTE LYMPHOBLASTIC LEUKEMIA; CANCER RESEARCH; CANCER THERAPY; CHEMOTHERAPY; CHROMOSOME ABERRATION; DNA BINDING; EXPERIMENTAL MODEL; FUSION GENE; GENE TRANSLOCATION; GENOME; HOX GENE; HUMAN; MOLECULAR GENETICS; MUTAGENESIS; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; TUMOR SUPPRESSOR GENE; ACUTE LYMPHOCYTIC LEUKEMIA; CHILD; COMPARATIVE STUDY; FEMALE; GENE EXPRESSION PROFILING; GENETIC PREDISPOSITION; GENETICS; HOSPITALIZATION; INFANT; MALE; MOLECULAR BIOLOGY; MUTATION; PRESCHOOL CHILD; PROGNOSIS; RISK ASSESSMENT; SENSITIVITY AND SPECIFICITY;

CHILD; CHILD, PRESCHOOL; CHROMOSOME ABERRATIONS; FEMALE; GENE EXPRESSION PROFILING; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INFANT; LEUKEMIA, LYMPHOCYTIC, ACUTE; MALE; MOLECULAR BIOLOGY; MUTATION; PROGNOSIS; PROTO-ONCOGENE PROTEINS; RISK ASSESSMENT; SENSITIVITY AND SPECIFICITY; SEVERITY OF ILLNESS INDEX;

EID: 27244440324     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.2005.05.047     Document Type: Review

References (126)

1. Rowley JD: The critical role of chromosome translocations in human leukemias. Annu Rev Genet 32:495-519, 1998
2. Armstrong SA, Staunton JE, Silverman LB, et al: MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 30:41-47, 2002
3. Yeoh EJ, Ross ME, Shurtleff SA, et al: Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1:133-143, 2002
4. Ferrando AA, Neuberg DS, Staunton J, et al: Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 1:75-87, 2002
5. Armstrong SA, Kung AL, Mabon ME, et al: Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell 3:173-183, 2003
6. Armstrong SA, Mabon ME, Silverman LB, et al: FLT3 mutations in childhood acute lymphoblastic leukemia. Blood 103:3544-3546, 2004
7. Weng AP, Ferrando AA, Lee W, et al: Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306:269-271, 2004
8. Kohlmann A, Schoch C, Schnittger S, et al: Pediatric acute lymphoblastic leukemia (ALL) gene expression signatures classify an independent cohort of adult ALL patients. Leukemia 18:63-71, 2004
9. Gaynon PS, Trigg ME, Heerema NA, et al: Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia 14:2223-2233, 2000
10. Maloney KW, Shuster JJ, Murphy S, et al: Long-term results of treatment studies for childhood acute lymphoblastic leukemia: Pediatric Oncology Group studies from 1986-1994. Leukemia 14:2276-2285, 2000
11. Schrappe M, Reiter A, Zimmermann M, et al: Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Munster. Leukemia 14:2205-2222, 2000
12. Silverman LB, Declerck L, Gelber RD, et al: Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995). Leukemia 14:2247-2256, 2000
13. Robison LL, Bhatia S: Late-effects among survivors of leukaemia and lymphoma during childhood and adolescence. Br J Haematol 122:345-359, 2003
14. Greaves MF, Wiemels J: Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 3:639-649, 2003
15. Golub TR, Barker GF, Lovett M, et al: Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 77:307-316, 1994
16. Golub TR, Barker GF, Stegmaier K, et al: Involvement of the TEL gene in hematologic malignancy by diverse molecular genetic mechanisms. Curr Top Microbiol Immunol 211:279-288, 1996
17. 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 84:321-330, 1996
18. Song WJ, Sullivan MG, Legare RD, et al: Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet 23:166-175, 1999
19. Dal Cin P, Atkins L, Ford C, et al: Amplification of AML1 in childhood acute lymphoblastic leukemias. Genes Chromosomes Cancer 30:407-409, 2001
20. Wang LC, Kuo F, Fujiwara Y, et al: Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL. EMBO J 16:4374-4383, 1997
21. Wang LC, Swat W, Fujiwara Y, et al: The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. Genes Dev 12:2392-2402, 1998
22. Hock H, Meade E, Medeiros S, et al: Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes Dev 18:2336-2341, 2004
23. Cave H, Cacheux V, Raynaud S, et al: ETV6 is the target of chromosome 12p deletions in t(12:21) childhood acute lymphocytic leukemia. Leukemia 11:1459-1464, 1997
24. McLean TW, Ringold S, Neuberg D, et al: TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia. Blood 88:4252-4258, 1996
25. Takeuchi S, Seriu T, Bartram CR, et al: TEL is one of the targets for deletion on 12p in many cases of childhood B-lineage acute lymphoblastic leukemia. Leukemia 11:1220-1223, 1997
26. 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 93:12359-12363, 1996
27. Wang Q, Stacy T, Binder M, et al: 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 93:3444-3449, 1996
28. Wang Q, Stacy T, Miller JD, et al: The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell 87:697-708, 1996
29. Niki M, Okada H, Takano H, et al: Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor. Proc Natl Acad Sci U S A 94:5697-5702, 1997
30. Borkhardt A, Cazzaniga G, Viehmann S, et al: Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials: Associazione Italians Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Munster Study Group. Blood 90:571-577, 1997
31. Rubnitz JE, Downing JR, Pui CH, et al: TEL gene rearrangement in acute lymphoblastic leukemia: A new genetic marker with prognostic significance. J Clin Oncol 15:1150-1157, 1997
32. Rubnitz JE, Pui CH, Downing JR: The role of TEL fusion genes in pediatric leukemias. Leukemia 13:6-13, 1999
33. Taketani T, Taki T, Sugita K, et al: FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy. Blood 103:1085-1088, 2004
34. Pui CH: Childhood leukemias-Current status and future perspective. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 36:322-327, 1995
35. Kamps MP, Look AT, Baltimore D: The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Genes Dev 5:358-368, 1991
36. Raimondi SC, Behm FG, Roberson PK, et al: Cytogenetics of pre-B-cell acute lymphoblastic leukemia with emphasis on prognostic implications of the t(1;19). J Clin Oncol 8:1380-1388, 1990
37. Mellentin JD, Murre C, Donlon TA, et al: The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias. Science 246:379-382, 1989
38. Nourse J, Mellentin JD, Galili N, et al: Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 60:535-545, 1990
39. Kamps MP, Murre C, Sun XH, et al: A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell 60:547-555, 1990
40. Sigvardsson M, O'Riordan M, Grosschedl R: EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. Immunity 7:25-36, 1997
41. Murre C, McCaw PS, Vaessin H, et al: Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58:537-544, 1989
42. Chang CP, Shen WF, Rozenfeld S, et al: Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes Dev 9:663-674, 1995
43. Erikson J, Finger L, Sun L, et al: Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias. Science 232:884-886, 1986
44. McKeithan TW, Shima EA, Le Beau MM, et al: Molecular cloning of the breakpoint junction of a human chromosomal 8;14 translocation involving the T-cell receptor alpha-chain gene and sequences on the 3′ side of MYC. Proc Natl Acad Sci USA 83:6636-6640, 1986
45. Shima EA, Le Beau MM, McKeithan TW, et al: Gene encoding the alpha chain of the T-cell receptor is moved immediately downstream of c-myc in a chromosomal 8;14 translocation in a cell line from a human T-cell leukemia. Proc Natl Acad Sci U S A 83:3439-3443, 1986
46. Begley CG, Aplan PD, Davey MP, et al: Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript. Proe Natl Acad Sci U S A 86:2031-2035, 1989
47. Chen Q, Cheng JT, Tasi LH, et al: The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein. EMBO J 9:415-424, 1990
48. Xia Y, Brown L, Yang CY, et al: TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia. Proc Natl Acad Sci U S A 88:11416-11420, 1991
49. Mellentin JD, Smith SD, Cleary ML: lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif. Cell 58:77-83, 1989
50. Baer R: TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell aeute leukaemia. Semin Cancer Biol 4:341-347, 1993
51. Hsu HL, Cheng JT, Chen Q, et al: Enhancer-binding activity of the tal-1 oncoprotein in association with the E47/E12 helix-loop-helix proteins. Mol Cell Biol 11:3037-3042, 1991
52. Bain G, Engel I, Robanus Maandag EC, et al: E2A deficiency leads to abnormalities in alphabeta T-cell development and to, rapid development of T-cell lymphomas. Mol Cell Biol 17:4782-4791, 1997
53. Yan W, Young AZ, Soares VC, et al: High incidence of T-cell tumors in E2A-null mice and E2A/ld1 double-knockout mice. Mol Cell Biol 17:7317-7327, 1997
54. Morrow MA, Mayer EW, Perez CA, et al: Overexpression of the helix-loop-helix protein Id2 blocks T cell development at multiple stages Mol Immunol 36:491-503, 1999
55. O'Neil J, Billa M, Oikemus S, et al: The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice. Oncogene 20:3897-3905, 2001
56. Chervinsky DS, Zhao XF, Lam DH, et al: Disordered T-cell development and T-cell malignancies in SCL LMO1 double-transgenic mice: Parallels with E2A-deficient mice. Mol Cell Biol 19:5025-5035, 1999
57. Aplan PD, Jones CA, Chervinsky DS, et al: An scl gene product lacking the transactivation domain induces bony abnormalities and cooperates with LMO1 to generate T-cell malignancies in transgenic mice. EMBO J 16:2408-2419, 1997
58. Boehm T, Foroni L, Kaneko Y, et al: The rhombotin family of cysteine-rich LIM-domain oncogenes: Distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc Natl Acad Sci U S A 88:4367-4371, 1991
59. Royer-Pokora B, Loos U, Ludwig WD: TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). Oncogene 6:1887-1893, 1991
60. Greenberg JM, Boehm T, Sofroniew MV, et al: Segmental and developmental regulation of a presumptive T-cell oncogene in the central nervous system. Nature 344:158-160, 1990
61. Valge-Archer VE, Osada H, Warren AJ, et al: The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells. Proc Natl Acad Sci U S A 91:8617-8621, 1994
62. Wadman I, Li J, Bash RO, et al: Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J 13:4831-4839, 1994
63. McGuire EA, Rintoul CE, Sclar GM, et al: Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukamia/lymphoms. Mol Cell Biol 12:4186-4196, 1992
64. Hacein-Bey-Abina S, von Kalle C, Schmidt M, et al: A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 348:255-256, 2003
65. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al: LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302:415-419, 2003
66. McCormack MP, Rabbitts TH: Activation of the T-cell oncogene LMO2 after gene therapy tor X-linked severe combined immunodeficiency. N Engl J Med 350:913-922, 2004
67. Dube ID, Kamel-Reid S, Yuan CC, et al: A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14). Blood 78:2996-3003, 1991
68. Hatano M, Roberts CW, Minden M, et al: Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. Science 253:79-82, 1991
69. Kennedy MA, Gonzalez-Sarmiento R, Kees UR, et al: HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24. Proc Natl Acad Sci USA 88:8900-8904, 1991
70. Lu M, Gong ZY, Shen WF, et al: The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukemia codes for a homeobox protein. EMBO J 10:2905-2910, 1991
71. Dear TN, Sanchez-Garcia I, Rabbitts TH: The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes. Proc Natl Acad Sci USA 90:4431-4435, 1993
72. Allen JD, Adams JM: Enforced expression of Hlx homeobox gene prompts myeloid cell maturation and altered adherence properties of T cells. Blood 81:3242-3251, 1993
73. McGinnis W, Krumlauf R: Homeobox genes and axial patterning. Cell 68:283-302, 1992
74. Roberts CW, Shutter JR, Korsmeyer SJ: Hox11 controls the genesis of the spleen. Nature 368:747-749, 1994
75. Berger R, Dastugue N, Busson M, et al: t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia: A collaborative study of the Groupe Francais de Cytogenetique Hematologique (GFCH). Leukemia 17:1851-1857, 2003
76. Cave H, Suciu S, Preudhomme C, et al: Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: Results of EORTC studies 58881 and 58951. Blood 103:442-450, 2004
77. Soulier J, Clappier E, Cayuela JM, et al: HOXA genes are included in genetic and biological networks defining human acute T-cell leukemia (T-ALL). Blood 106:274-286, 2005
78. Rubnitz JE, Camitta BM, Mahmoud H, et al: Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19) (q23;p13.3) translocation. J Clin Oncol 17:191-196, 1999
79. Ferrando AA, Armstrong SA, Neuberg DS, et al: Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: Dominance of HOX dysregulation. Blood 102:262-268, 2003
80. Dreyling MH, Martinez-Climent JA, Zheng M, et al: The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family. Proc Natl Acad Sci U S A 93:4804-4809, 1996
81. Narita M, Shimizu K, Hayashi Y, et al: Consistent detection of CALM-AF10 chimaeric transcripts in haematological malignancies with t(10;11)(p13;q14) and identification of novel transcripts. Br J Haematol 105:928-937, 1999
82. Kobayashi H, Hosoda F, Maseki N, et al: Hematologic malignancies with the t(10;11) (p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes. Genes Chromosomes Cancer 20:253 259, 1997
83. Jones LK, Chaplin T, Shankar A, et al: Identification and molecular characterisation of a CALM-AF10 fusion in acute megakaryoblastic leukaemia. Leukemia 15:910-914, 2001
84. Carlson KM, Vignon C, Bohlander S, et al: Identification and molecular characterization of CALM/AF10fusion products in T cell acute lymphoblastic leukemia and acute myeloid leukemia. Leukemia 14:100-104, 2000
85. Asnafi V, Radford-Weiss I, Dastugue N, et al: CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage. Blood 102:1000-1006, 2003
86. Ellisen LW, Bird J, West DC, et al: TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66:649-661, 1991
87. Rand MD, Grimm LM, Artavanis-Tsakonas S, et al: Calcium depletion dissociates and activates heterodimeric notch receptors. Mol Cell Biol 20:1825-1835, 2000
88. Sanchez-Irizarry C, Carpenter AC, Weng AP, et al: Notch subunit heterodimerization and prevention of ligand-independent proteolytic activation depend, respectively, on a novel domain and the LNR repeats. Mol Cell Biol 24:9265-9273, 2004
89. Kimberly WT, Esler WP, Ye W, et al: Notch and the amyloid precursor protein are cleaved by similar gamma-secretase(s). Biochemistry 42: 137-144, 2003
90. Aster JC, Xu L, Karnell FG, et al: Essential roles for ankyrin repeat and transactivation domains in induction of T-cell leukemia by notch1. Mol Cell Biol 20:7505-7515, 2000
91. Hoemann CD, Beaulieu N, Girard L, et al: Two distinct Notch1 mutant alleles are involved in the induction of T-cell leukemia in c-myc transgenic mice. Mol Cell Biol 20:3831-3842, 2000
92. Feldman BJ, Hampton T, Cleary ML: A carboxy-terminal deletion mutant of Notch1 accelerates lymphoid oncogenesis in E2A-PBX1 transgenic mice. Blood 96:1906-1913, 2000
93. Biondi A, Cimino G, Pieters R, et al: Biological and therapeutic aspects of infant leukemia. Blood 96:24-33, 2000
94. Chen CS, Sorensen PH, Domer PH, et al: Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood 81:2386-2393, 1993
95. Domer PH, Fakharzadeh SS, Chen CS, et al: Acute mixed-lineage leukemia t(4;11) (q21;q23) generates an MLL-AF4 fusion product. Proc Natl Acad Sci U S A 90:7884-7888, 1993
96. 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 71:701-708, 1992
97. Tkachuk DC, Kohler S, Cleary ML: Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell 71:691-700, 1992
98. 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 88:10735-10739, 1991
99. Ayton PM, Cleary ML: Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 20:5695-5707, 2001
100. Milne TA, Briggs SD, Brock HW, et al: MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell 10:1107-1117, 2002
101. Nakamura T, Mori T, Tada S, et al: ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell 10:1119-1128, 2002
102. Hsieh JJ, Ernst P, Erdjument-Bromage H, et al: Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization. Mol Cell Biol 23:186-194, 2003
103. Hsieh JJ, Cheng EH, Korsmeyer SJ: Taspasel: A threonine aspartase required for cleavage of MLL and proper HOX gene expression. Cell 115:293-303, 2003
104. Yokoyama A, Kitabayashi I, Ayton PM, et al: Leukemia proto-oncoprotein MLL is proteolytically processed into 2 fragments with opposite transcriptional properties. Blood 100:3710-3718, 2002
105. Hess JL, Yu BD, Li B, et al: Defects in yolk sac hematopoiesis in Mll-null embryos. Blood 90:1799-1806, 1997
106. Yu BD, Hess JL, Horning SE, et al: Altered Hox expression and segmental identity in Mll-mutant mice. Nature 378:505-508, 1995
107. Ernst P, Fisher JK, Avery W, et al: Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell 6:437-443, 2004
108. Ernst P, Mabon M, Davidson AJ, et al: An Mll-dependent Hox program drives hematopoietic progenitor expansion. Curr Biol 14:2063-2069, 2004
109. Owens BM, Hawley RG: HOX and non-HOX homeobox genes in leukemic hematopoiesis. Stem Cells 20:364-379, 2002
110. 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 12:159-167, 1996
111. Nakamura T, Largaespada DA, Lee MP, et al: Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet 12:154-158, 1996
112. Gilliland DG, Griffin JD: The roles of FLT3 in hematopoiesis and leukemia. Blood 100:1532-1542, 2002
113. Brown P, Levis M, Shurtleff S, et al: FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression. Blood 105:812-820, 2005
114. Ribeiro RC, Abromowitch M, Raimondi SC, et al: Clinical and biologic hallmarks of the Philadelphia chromosome in childhood acute lymphoblastic leukemia. Blood 70:948-953, 1987
115. Crist W, Carroll A, Shuster J, et al: Philadelphia chromosome positive childhood acute lymphoblastic leukemia: Clinical and cytogenetic characteristics and treatment outcome-A Pediatric Oncology Group study. Blood 76:489-494, 1990
116. Fletcher JA, Lynch EA, Kimball VM, et al: Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia. Blood 77: 435-439, 1991
117. Arico M, Valsecchi MG, Camitta B, et al: Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 342:998-1006, 2000
118. Ferrando AA, Neuberg DS, Dodge RK, et al: Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet 363:535-536, 2004
119. Druker BJ, Talpaz M, Resta DJ, et al: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031-1037, 2001
120. Demetri GD, von Mehren M, Blanke CD, et al: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472-480, 2002
121. Paez JG, Janne PA, Lee JC, et al: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304:1497-1500, 2004
122. Sordella R, Bell DW, Haber DA, et al: Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305:1163-1167, 2004
123. Druker BJ: Imatinib as a paradigm of targeted therapies. Adv Cancer Res 91:1-30, 2004
124. Ottmann OG, Druker BJ, Sawyers CL, et al: A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 100:1965-1971, 2002
125. Thomas DA, Faderl S, Cortes J, et al: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103:4396-4407, 2004
126. Gorre ME, Mohammed M, Ellwood K, et al: Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:876-880, 2001