Molecular basis of leukemogenesis

Current Opinion in Hematology

Volumn 5, Issue 4, 1998, Pages 264-270

  Rubnitz, Jeffrey E ^a   Look, A Thomas ^b  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL EXPERIMENT; ANIMAL MODEL; CHROMOSOME TRANSLOCATION; GENE REARRANGEMENT; HEMATOPOIESIS; HUMAN; LEUKEMOGENESIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 0032427928     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199807000-00006     Document Type: Review

References (60)

1. Look AT: Oncogenic transcription factors in the human acute leukemias. Science 1997, 278:1059-1064.
2. Waring PM, Cleary ML: Disruption of a homolog of trithorax by 11q23 translocations: leukemogenic and transcriptional implications. Curr Top Microbiol Immunol 1997, 220:1-23.
3. Hillion J, Le Coniat M, Jonveaux P, Berger R, Bernard OA: AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood 1997, 90:3714-3719.
4. Taki T, Sako M, Tsuchida M, Hayashi Y: The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene. Blood 1997, 89:3945-3950.
5. So CW, Caldas C, Liu MM, Chen SJ, Huang QH, Gu LJ, Sham MH, Wiedemann LM, Chan LC: EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human leukemia. Proc Natl Acad Sci U S A 1997, 94:2563-2568.
6. Hess JL, Yu BD, Li B, Hanson R, Korsmeyer SJ: Defects in yolk sac hematopoiesis in Mll-null embryos. Blood 1997, 90:1799-1806.
7. Butler LH, Slany R, Cui X, Cleary ML, Mason DY: The HRX proto-oncogene product is widely expressed in human tissues and localizes to nuclear structures. Blood 1997, 89:3361-3370.
8. Lavau C, Szilvassy SJ, Slany R, Cleary ML: Immortalization and leukemic •• transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. EMBO J 1997, 16:4226-4237. The authors used retroviral gene transfer to express HRX-ENL in hematopoietic stem cells. The fusion protein immortalized myeloid precursors, which subsequently induced AML
9. 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. 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.
11. Sasaki K, Yagi H, Bronson RT, Tominaga K, Matsunashi T, Deguchi K, 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, 93:12359-12363.
12. Wang Q, Stacy T, Miller JD, Lewis AF, Gu TL, Huang X, et al.: The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell 1996,87:697-708.
13. Niki M, Okada H, Takano H, Kuno J, Tani K, Hibino 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 1997, 94:5697-5702. Homozygous disruption of the gene encoding CBFβ resulted in defective liver hematopoiesis, indicating that CBFβ is required for AML1 -CBFβ function in vivo.
14. Castilla LH, Wijmenga C, Wang Q, Stacy T, Speck NA, Eckhaus M, et al: Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Cell 1996, 87:687-696.
15. Yergeau DA, Hetherington CJ, Wang Q, Zhang P, Sharpe AH, Binder M, •• et al.: Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1 -ETO fusion gene. Nat Genet 1997, 15:303-306. Using knock-in technology, the authors show that AML1-ETO exerts a dominant negative effect on AML1 function, resulting in impaired liver hematopoiesis.
16. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci • L, 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. Blood 1997, 90:571-577. The TEL-AML1 fusion occurred in 22% of B-lineage ALL cases and was associated with an event-free survival of 90% at 4 years.
17. Rubnitz JE, Behm FG, Pui C-H, Evans WE, Relling MV, Raimondi SC, et al.: Genetic studies of childhood acute lymphoblastic leukemia with emphasis on p16, MLL, and ETV6 gene abnormalities: results of St. Jude Total therapy Study XII. Leukemia 1997, 11:1201-1206.
18. Rubnitz JE, Downing JR, Pui C-H, Shurtleff SA, Raimondi SC, Evans WE, • et al.: TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J Clin Oncol 1997, 15:1150-1157. TEL gene rearrangements were detected in one fourth of B-lineage ALL cases and were associated with an excellent outcome. TEL rearrangement was shown to be a favorable prognostic factor independent of age and leukocyte count.
19. 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, 77:307-316.
20. Papadopoulos P, Ridge SA, Boucher CA, Stocking C, Wiedemann LM: The novel activation of ABL by fusion to an ets-related gene, TEL. Cancer Res 1995, 55:34-38.
21. Buijs A, Sherr S, van Baal S, van Bezouw S, van der Ras D, Geurts van Kessel A, et al.: Translocation (12:22)(p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11. Oncogene 1995, 10:1511-1519.
22. Peelers P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, et al.: Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997, 90:2535-2540.
23. Berger R, Le Coniat M, Lacronique V, Daniel M-T, Lessard M, Berthou C, et al.: Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene. Leukemia 1997, 11:1400-1403.
24. Cave H, Cacheux V, Raynaud S, Brunie G, Bakkus M, Cochaux P, et al.: ETV6 is the target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia. Leukemia 1997, 11:1459-1464.
25. Takeuchi S, Seriu T, Bartram CR, Golub TR, Reiter A, Miyoshi I, et al.: TEL is one of the targets for deletion on 12p in many cases of childhood B-lineage acute lymphoblastic leukemia. Leukemia 1997, 11:1220-1223.
26. Golub TR, Barker GF, Stegmaier K, Gilliland DG: The TEL gene contributes to the pathogenesis of myeloid and lymphoid leukemias by diverse molecular genetic mechanisms. Curr Top Microbiol Immunol 1997, 220:67-79.
27. Hiebert SW, Sun W, Davis JN, Golub T, Shurtleff S, Buijs A, et al.: The t(12;21 ) translocation converts AML-1B from an activator to a repressor of transcription. Mol Cell Biol 1996, 16:1349-1355.
28. Jousset C, Carron C, Boureux A, Quang CT, Oury C, Dusanter-Fourt I, et al.: A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFRb oncoprotein. EMBO J 1997, 16:69-82.
29. McLean TW, Ringold S, Neuberg D, Stegmaier K, Tantravahi R, Ritz J, et al.: TEL/AML1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia. Blood 1996, 88:4252-4258.
30. Wang LC, Kuo F, Fujiwara Y, Gilliland DG, Golub TR, Orkin SH: Yolk sac •• angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL. EMBO J 1997, 16:4374-4383. The targeted disruption of TEL caused defective yolk sac angiogenesis and death on day 11 of embryogenesis.
31. Grisolano JL, Wesselschmidt RL, Ley TJ: Altered myeloid development and acute leukemia in transgenic mice expressing PML-RARa under control of cathepsin G regulatory sequences. Blood 1997, 89:376-387.
32. He L-Z, Tribioli C, Rivi R, Peruzzi D, Pelicci PG, Soares V, Cattoretti G, Pandolfi PP: Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice. Proc Natl Acad Sci U S A 1997, 94:5302-5307.
33. Brown D, Kogan S, Lagasse E, Weissman I, Alcalay M, Pelicci PG, et al.: • A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. Proc Natl Acad Sci U S A 1997, 94:2551-2556. This paper independently reports the effects of PML-RARα expression in early myeloid cells of transgenic mice. PML-RARα induced abnormal myeloid development and subsequent AML
34. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, •• Ogden A, et al.: All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997, 337:1021-1028. In a large randomized trial of acute promyelocytic leukemia, ATRA treatment improved disease-free and overall survival compared to chemotherapy alone.
35. 3 caused rapid degradation of PML-RARα proteins and had dose-dependent effects on APL cells, inducing partial differentiation at low concentrations and apoptosis at higher concentrations.
36. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, et al.: Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997, 89:3354-3360. Arsenic trioxide was shown to be effective at inducing remission in relapsed APL patients refractory to ATRA and chemotherapy.
37. Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, et al.: In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 1996, 88:1052-1061.
38. Zhu J, Koken MH, Quignon F, Chelbi-Alix MK, Degos L, Wang ZY, Chen Z, de TH: Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia. Proc Natl Acad Sci U S A 1997, 94:3978-3983.
39. Chang CP, deVivo I, Cleary ML: The Hox cooperativity motif of the • chimeric oncoprotein E2a-Pbx1 is necessary and sufficient for oncogenesis. Mol Cell Biol 1997, 17:81-88. The authors demonstrate that a conserved motif adjacent to the homeodomain of PBX1 is required for transactivation and transformation by E2A-PBX1.
40. Chang CP, Shen WF, Rozenfeld S, Lawrence HJ, Largman C, Cleary ML: Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes Dev 1995, 9:663-674.
41. Lu Q, Kamps MP: Heterodimerization of Hox proteins with Pbx1 and oncoprotein E2a-Pbx1 generates unique DNA-binding specificities at nucleotides predicted to contact the N-terminal arm of the Hox homeodomain: demonstration of Hox-dependent targeting of E2a-Pbx1 in vivo. Oncogene 1997, 14:75-83.
42. Chang CP, Jacobs Y, Nakamura T, Jenkins NA, Copeland NG, Cleary ML: Meis proteins are major in vivo DNA binding partners for wild-type but not chimeric Pbx proteins. Mol Cell Biol 1997, 17:5679-5687.
43. Fu X, Kamps MP: E2a-Pbx1 induces aberrant expression of tissue specific and developmentally regulated genes when expressed in NIH 3T3 fibroblasts. Mol Cell Biol 1997, 17:1503-1512.
44. Dedera DA, Waller EK, LeBrun DP, Sen-Majumdar A, Stevens ME, Barsh GS, Cleary ML: Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice. Cell 1993, 74:833-843.
45. Monica K, LeBrun DP, Dedera DA, Brown R, Cleary ML: Transformation properties of the E2A-PBX1 chimeric oncoprotein: fusion with E2A is essential, but the PBX1 homeodomain is dispensable. Mol Cell Biol 1994, 14:8304-8314.
46. Smith KS, Jacobs Y, Chang CP, Cleary ML: Chimeric oncoprotein E2a-Pbx1 induces apoptosis of hematopoietic cells by a p53-independent mechanism that is suppressed by Bcl-2. Oncogene 1997, 14:2917-2926.
47. Inaba T, Inukai T, Yoshihara T, Seyschab H, Ashmun RA, Canman CE, Laken SJ, Kastan MB, Look AT: Reversal of apoptosis by the leukaemia associated E2A-HLF chimaeric transcription factor. Nature 1996, 382:541-544.
48. Inukai T, Inaba T, Yoshihara T, Look AT: Cell transformation mediated by • homodimeric E2A-HLF transcription factors. Mol Cell Biol 1997, 17:1417-1424. The results of this study support a model in which E2A-HLF transforms cells by binding DNA as a homodimer and altering the expression of downstream genes.
49. Look AT: E2A-HLF chimeric transcription factors in pro-B cell acute lymphoblastic leukemia. Curr Top Microbiol Immunol 1997, 220:45-53.
50. Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, 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 1996, 12:154-158.
51. Borrow J, Shearman AM, Stanton VP Jr, Becher R, Collins T, Williams AJ, et al.: The t(7;11 )(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9 [see comments]. Nat Genet 1996, 12:159-167.
52. Lawrence HJ, Helgason CD, Sauvageau G, Fong S, Izon DJ, Humphries RK, Largman C: Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erytbroid, and lymphoid hematopoiesis. Blood 1997, 89:1922-1930.
53. Thorsteinsdottir U, Sauvageau G, Hough MR, Dragowska W, Lansdorp • PM, Lawrence HJ, et al.: Overexpression of HOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia. Mol Cell Biol 1997, 17:495-505. A role for HOX genes in normal hematopoiesis and in leukemogenesis is supported by the development of AML following overexpression of HOXA10,
54. Sauvageau G, Thorsteinsdottir U, Hough MR, Hugo P, Lawrence HJ, Largman C, Humphries RK: Overexpression of HOXB3 in hematopoietic cells causes defective lymphoid development and progressive myeloproliferation. Immunity 1997, 6:13-22.
55. Levine AJ: P53, the cellular gatekeeper for growth and division. Cell 1997, 88:323-331.
56. ARF is a bona fide tumor-suppressor gene. The INK4a locus thus encodes two distinct tumor-suppressor proteins that likely act in different tumor types.
57. Haber DA: Splicing into senescence: the curious case of p16 and P19ARF. Cell 1997, 91:555-558.
58. Serrano M, Lee H, Chin L, Cordon-Cardo C, Beach D, DePinho RA: Role of the INK4a locus in tumor suppression and cell mortality. Cell 1996, 85:27-37.
59. Rubnitz JE, Pui C-H: Recent advances in the biology and treatment of childhood acute lymphoblastic leukemia. Curr Opin Hematol 1997, 4:233-241.
60. Gottesfeld JM, Neely L, Trauger JW, Baird EE, Dervan PB: Regulation of gene expression by small molecules. Nature 1997, 387:202-205.