The role of HOX genes in myeloid leukemogenesis

Current Opinion in Hematology

Volumn 13, Issue 2, 2006, Pages 67-73

  Eklund, Elizabeth A ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Gene transcription; Hox; Leukemogenesis; Myelopoiesis

Indexed keywords

GENE PRODUCT; HOX PROTEIN; TRANSCRIPTION FACTOR;

BONE MARROW CANCER; GENE CONTROL; GENE EXPRESSION PROFILING; GENE FUNCTION; GENE IDENTIFICATION; GENE OVEREXPRESSION; HEMATOPOIESIS; HEMATOPOIETIC CELL; HIGH THROUGHPUT SCREENING; HOX GENE; HUMAN; LEUKEMOGENESIS; MYELOID LEUKEMIA; MYELOPOIESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROCESSING; REVIEW; TRANSCRIPTION REGULATION;

ANIMALS; GENES, HOMEOBOX; HOMEODOMAIN PROTEINS; HUMANS; LEUKEMIA, MYELOID; MICE; MODELS, ANIMAL; MYELOPOIESIS; TRANSCRIPTION, GENETIC;

EID: 33646786144     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/01.moh.0000208467.63861.d6     Document Type: Review

References (68)

1. Levine M, Rubin GM, Tjian R. Human DNA sequences homologous to a protein coding region conserved between homeotic genes of Drosophila. Cell 1984; 38:667-673.
2. Acampora D, D'Esposito M, Faiella A, et al. The human HOX gene family. Nucleic Acids Res 1989; 17:10385-10402.
3. Duboule E, Dolle P. The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J 1989; 8:1497-1505.
4. Akam M. HOX and HOM: homologous gene clusters in insects and vertebrates. Cell 1989; 57:347-349.
5. Sauvageau G, Lansdorp PM, Caves CJ, et al. Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc Natl Acad Sci U S A 1994; 91:12223-12227.
6. Vieille-Grosjean I, Roullot V, Courtos G. Identification of homeobox-containing genes expressed in hematopoietic blast cells. Biochem Biophys Res Commun 1992; 185:785-792.
7. Moretti P, Simmons P, Thomas P, et al. Identification of homeobox gene expressed in human haemopoietic progenitor cells. Gene 1994; 144:213-219.
8. Sauvageau G, Thorsteinsdottir U, Eaves CJ, et al. Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev 1995; 9:1753-1765.
9. Fujino T, Uamazaki Y, Largaespada DA, et al. Inhibition of myeloid differentiation by HoxA9, Hoxb8 and Meis homeobox genes. Exp Hematol 2001; 29:856-863.
10. Drabkin HA, Parsy C, Gerguson K, et al. Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia. Leukemia 2002; 16:186-195.
11. Giampaolo A, Felli N, Diverio D, et al. Expression pattern of HOXb6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia. Leukemia 2002; 16:1293-1301.
12. Golub TR, Slonim DK, Tamayo P, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999; 286:531-537.
13. Lawrence HJ, Sauvageau G, Ahmadi N, et al. Stage and lineage specific expression of the HOXA10 homeobox gene in normal and leukemic hematopoietic cells. Exp Hematol 1995; 23:1160-1166.
14. Lawrence HJ, Helgason CD, Sauvageau G, et al. Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis. Blood 1997; 89:1922-1930.
15. Kappen C. Disruption of the homeobox gene hoxb6 in mice results in increased numbers of early erythrocyte progenitors. Am J Hematol 2000; 65:111-118.
16. Satokata I, Benson G, Mass R. Sexually dimorphic sterility phenotypes in HOXA10 deficient mice. Nature 1995; 374:460-463.
17. Calvo KR, Sykes DB, Pasillas M, Kamps MP. HoxA9 immortalizes a granulocyte macrophage colony stimulating factor dependent promyelocyte capable of biphenotypic differentiation to neutrophils or macrophages independent of enforced Meis expression. Mol Cell Biol 2000; 20:3274-3285.
18. Schnabel CA, Jacobs Y, Cleary ML. HoxA9 mediated immortalization of myeloid progenitors requires functional interactions with TALE cofactors Pbx and Meis. Oncogene 2000; 19:608-616.
19. Calvo KR, Koepfler PS, Sykes DB, et al. Meis1a suppresses differentiation by G-CSF and promotes proliferation by SCF: potential mechanisms of cooperativity with HoxA9 in myeloid leukaemia. PNAS 2001; 98:13120-13125.
20. Buske C, Feuring-Buske M, Antonchuk J, et al. Overexpression of HOXA10 perturbs human lymphomyelopoiesis in vitro and in vivo. Blood 2001; 97:2286-2292.
21. Kroon E, Krosl J, Thorsteinsdottir U, et al. HoxA9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b. EMBO J 1998; 17:3714-3725.
22. Thorsteinsdottir U, Mamo A, Kroon E, et al. Overexpression of the myeloid leukemia associated HoxA9 gene in bone marrow cells induces stem cell expansion. Blood 2002; 99:121-129.
23. Thorsteinsdottir U, Kroon E, Jerome L, et al. Defining roles of HOX and MEIS1 genes in induction of acute myeloid leukemia. Mol Cell Biol 2001; 21:224-234.
24. Thorsteinsdottir U, Sauvageau G, Hough MR, 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.
25. Chang CP, Brocchieri L, Shen WF, et al. Pbx modulation of hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the HOX locus. Mol Cell Biol 1996; 16:1734-1745.
26. Shen WF, Rozenfeld S, Lawrence HJ, Largman C. The Abd-B-like hox homeodomain proteins can be subdivided by the ability to form complexes with Pbx1a on a novel DNA target. J Biol Chem 1997; 272:8198-8206.
27. Neuteboom STC, Murre C. Pbx raises the DNA binding specificity but not the selectivity of antennapedia Hox proteins. Mol Cell Biol 1997; 17:4696-4706.
28. Asahara H, Dutta S, Kao HY, et al. Pbx-Hox heterodimers recruit coactivator-corepressor complexes in an isoform-specific manner. Mol Cell Biol 1999; 19:8219-8225.
29. Shen WF, Montgomery JC, Rozenfeld S, et al. AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins. Mol Cell Biol 1997; 17:6448-6458.
30. Shen WF, Rozenfeld S, Kwong A, et al. HoxA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells. Mol Cell Biol 1999; 19:3051-3061.
31. Fischbach NA, Rozenfeld S, Shen WF, et al. HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo. Blood 2005; 105:1456-1466.
32. Kim MH, Chang HH, Shin C, et al. Genomic structure and sequence analysis of human HOXA9. DNA Cell Biol 1998; 17:407-414.
33. Lowney P, Corral J, Detmer K, et al. A human Hox 1 homeobox gene exhibits myeloid specific expression of alternative transcripts in human hematopoietic cells. Nucleic Acids Res 1991; 19:3443-3449.
34. Chang CP, Shen WF, Rozenfeld S, et al. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes Dev 1995; 9:663-674.
35. Ghannam G, Takeda A, Camarata T, et al. The oncogene Nup98-HOXA9 induces gene transcription in myeloid cells. J Biol Chem 2004; 279:866-875. Use of high throughput techniques to identify the transcriptome of HoxA9 and Nup98-HoxA9.
36. Ferrell CM, Dorsam ST, Ohta H, et al. Activation of stem cell specific genes by HOXA9 and HOXA10 homeodomain proteins in CD34+ human cord blood cells. Stem Cells 2005; 23:644-655. High throughput screening technique to identify differences in HoxA9 and HoxA10 transe riptomes.
37. Dorsam ST, Ferrell CM, Dorsam GP, et al. The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells. Blood 2004; 103:1676-1684.
38. Shi X, Bai S, Li L, Cao X. HoxA9 represses transforming growth factor β induced osteopontin gene transcription. J Biol Chem 2001; 276:850-855.
39. Bei L, Lu YF, Eklund EA. HoxA9 activates transcription of the gene encoding gp91phox during myeloid differentiation. J Biol Chem 2005; 280:12359-12370.
40. Eklund EA, Jalava A, Kakar R. Tyrosine phosphorylation decreases HoxA10 DNA-binding and transcriptional repression during IFNg induced differentiation in myeloid cell lines. J Biol Chem 2000; 275:20117-20126.
41. Lu Y, Goldenberg I, Bei L, et al. HoxA10 represses gene transcription in undifferentiated myeloid cells by interaction with histone deacetylase 2. J Biol Chem 2003; 278:47792-47802.
42. PHOX in phagocytic cells. J Immunol (in press).
43. Bromleigh VC, Freedman LP. P21 is a transcriptional target of HOXA10 in differentiating myelomonocytic cells. Genes Dev 2000; 14:2581-2586.
44. Saleh M, Rambaldi I, Yang XJ, Featherstone MS. Cell signaling switches HOX-PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases. Mol Cell Biol 2000; 20:8623-8633.
45. 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; 88:10735-10739.
46. Djabali M, Selleri L, Parry P, et al. A trithorax like gene is interrupted by chromosome 11q23 translocation in acute leukaemias. Nat Genet 1992; 2:113-118.
47. Gu Y, Nakamura Y, Alder H, et al. The (t94:11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4gene. Cell 1992; 71:701-708.
48. Lavau C, Du C, Thirman M, Zeleznik-Le N. Chromatin related properties of CBP fused to MLL generate a myelodysplastic like syndrome that evolves into myeloid leukaemia. EMBO J 2000; 19:4655-4664.
49. 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; 21:5678-5687.
50. Suzukawa K, Shimizu S, Nemoto N, et al. Identification of a chromosomal breakpoint and detection of a novel form of an MLL-AF17 fusion transcript in acute monocytic leukemia with t(11;17)(123;21). Int J Hematol 2005; 82:38-41.
51. Armstrong SA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 2002; 30:41-47.
52. Lavau C, Luo RT, Cu 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; 26:10984-10989.
53. Kumar AR, Hudson WA, Chen W, et al. HoxA9 influences the phenotype but not the incidence of MLL-AF9 fusion gene leukemia. Blood 2004; 103:1823-1828.
54. So CW, Karsunky H, Passegue E, et al. MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell 2003; 3:161-171.
55. So CW, Karsunky H, Wong P, et al. Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of HoxA7 or HoxA9. Blood 2004; 103:3192-3199. Indicates the complexity of the Hox code for leukemogenesis.
56. Milne TA, Briggs SD, Brock HW, et al. MLL targets SET domain methyltransferase activity of HOX gene promoters. Mol Cell 2002; 10:1107-1117.
57. Zeleznik-Le NJ, Harden AM, Rowley JD. 11q23 translocations split the 'AT-hood' cruciform DNA binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci U S A 1994; 91:10610-10614.
58. Zeisig BB, Schreiner S, Garcia-Cuellar PM, Slany RK. Transcriptional activation is the function encoded by MLL fusion partners. Leukemia 2003; 17:359-365.
59. Vijapurkar U, Fischbach N, Shen W, et al. Protein kinase C mediated phosphorylation of leukemia associated HOXA9 protein impairs its DNA binding ability and induces myeloid differentiation. Mol Cell Biol 2004; 24:3827-3837. Indicates the importance of posttranslational modification for Hox protein function.
60. Eklund EA, Goldenberg I, Lu Y, et al. SHP1 protein tyrosine phosphatase regulates HoxA10 DNA-binding and transcriptional repression activity in undifferentiated myeloid cells. J Biol Chem 2002; 39:36878-36888.
61. Van Zant G, Shultz L. Hematologic abnormalities of the immuno deficient mouse mutant, viable moth eaten (mev). Exp Hematol 1989; 17:81-87.
62. Nakamura T, Largaespada DA, Lee MP, et al. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosomal translocation t(7;11)(p15;p15) in human myeloid leukemia. Nat Genet 1996; 12:154-158.
63. Borrow J, Shearman AM, Stanton VP, 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; 12:159-167.
64. Hatano Y, Miura I, Nakamura T, et al. Molecular heterogeneity of the NUP98/HOXA9 fusion transcript in myelodysplastic syndromes associated with t(7;11)(p15;p15). Br J Haematol 1999; 107:600-604.
65. Yamamoto K, Nakamura Y, Nakamura Y, et al. Expression of the NUP98/ HOXA9 fusion transcript in the blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia with t(7;11)(p15;p15). Br J Haematol 2000; 109:423-426.
66. Calvo KR, Sykes DB, Pasillas MP, Kamps MP. Nup98-HoxA9 immortalizes myeloid progenitors, enforces expression of HoxA9, HoxA7 and Meis1, and alters cytokine-specific responses in a manner similar to that induced by retroviral co-expression of HoxA9 and Meis1. Oncogene 2002; 21:4247-4256.
67. Kroon E, Thorsteinsdottir U, Mayotte N, et al. Nup98-HOXA9 expression in hematopoietic stem cells induces chronic and acute myeloid leukemias in mice. EMBO J 2001; 20:350-361.
68. Iwasake M, Kuwata T, Yamazaki Y, et al. Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model. Blood 2005; 15:784-793. Elegant use of murine models to study cooperative leukemogenesis related to Nup98-HoxA9 fusion protein expression.