Hox genes in hematopoiesis and leukemogenesis

Oncogene

Volumn 26, Issue 47, 2007, Pages 6766-6776

  Argiropoulos, B ^a   Humphries, R K ^a,b  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Leukemic stem cells; Mll; NUP98 HOX; Self renewal

Indexed keywords

HYBRID PROTEIN;

CARCINOGENICITY; CELL RENEWAL; CELL TRANSFORMATION; FUSION GENE; GENE CONTROL; GENE EXPRESSION PROFILING; GENE FUNCTION; GENE LOCUS; GENE TARGETING; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HOX GENE; HUMAN; LEUKEMOGENESIS; MLL GENE; NUP98 GENE; PRIORITY JOURNAL; REVIEW;

ANIMALS; GENES, HOMEOBOX; HEMATOPOIESIS; HOMEODOMAIN PROTEINS; HUMANS; LEUKEMIA;

MURINAE;

EID: 35348849015     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/sj.onc.1210760     Document Type: Review

References (140)

1. Afonja O, Smith Jr JE, Cheng DM, Goldenberg AS, Amorosi E, Shimamoto T et al. (2000). MEIS1 and HOXA7 genes in human acute myeloid leukemia. Leuk Res 24: 849-855.
2. Alcalay M, Tiacci E, Bergomas R, Bigerna B, Venturini E, Minardi SP et al. (2005). Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc + AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance. Blood 106: 899-902.
3. Amsellem S, Pflumio F, Bardinet D, Izac B, Charneau P, Romeo PH et al. (2003). Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein. Nat Med 9: 1423-1427.
4. Antonchuk J, Sauvageau G, Humphries RK. (2001). HOXB4 overexpression mediates very rapid stem cell regeneration and competitive hematopoietic repopulation. Exp Hematol 29: 1125-1134.
5. Antonchuk J, Sauvageau G, Humphries RK. (2002). HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 109: 39-45.
6. Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD et al. (2002). MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 30: 41-47.
7. Ayton PM, Cleary ML. (2003). Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9. Genes Dev 17: 2298-2307.
8. Bai XT, Gu BW, Yin T, Niu C, Xi XD, Zhang J et al. (2006). Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats. Cancer Res 66: 4584-4590.
9. Bansal D, Scholl C, Frohling S, McDowell E, Lee BH, Dohner K et al. (2006). Cdx4 dysregulates Hox gene expression and generates acute myeloid leukemia alone and in cooperation with Meis1a in a murine model. Proc Natl Acad Sci USA 103: 16924-16929.
10. Bergeron J, Clappier E, Cauwelier B, Dastugue N, Millien C, Delabesse E et al. (2006). HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation. Leukemia 20: 1184-1187.
11. Beslu N, Krosl J, Laurin M, Mayotte N, Humphries KR, Sauvageau G. (2004). Molecular interactions involved in HOXB4-induced activation of HSC self-renewal. Blood 104: 2307-2314.
12. Bhardwaj G, Murdoch B, Wu D, Baker DP, Williams KP, Chadwick K et al. (2001). Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol 2: 172-180.
13. Bijl J, Thompson A, Ramirez-Solis R, Krosl J, Grier DG, Lawrence HJ et al. (2006). Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells. Blood 108: 116-122.
14. Bjornsson JM, Larsson N, Brun AC, Magnusson M, Andersson E, Lundstrom P et al. (2003). Reduced proliferative capacity of hematopoietic stem cells deficient in Hoxb3and Hoxb4. Mol Cell Biol 23: 3872-3883.
15. Blair A, Hogge DE, Sutherland HJ. (1998). Most acute myeloid leukemia progenitor cells with long-term proliferative ability in vitro and in vivo have the phenotype CD34(+)/CD71(-)/HLA-DR. Blood 92: 4325-4335.
16. Bonnet D, Dick JE. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730-737.
17. Brun AC, Bjornsson JM, Magnusson M, Larsson N, Leveen P, Ehinger M et al. (2004). Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells. Blood 103: 4126-4133.
18. Buske C, Feuring-Buske M, Abramovich C, Spiekermann K, Eaves CJ, Coulombel L et al. (2002). Deregulated expression of HOXB4 enhances the primitive growth activity of human hematopoietic cells. Blood 100: 862-868.
19. Calvo KR, Sykes DB, Pasillas MP, Kamps MP. (2002). 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 21: 4247-4256.
20. Camos M, Esteve J, Jares P, Colomer D, Rozman M, Villamor N et al. (2006). Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res 66: 6947-6954.
21. Cauwelier B, Cave H, Gervais C, Lessard M, Barin C, Perot C et al. (2007). Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogenetique Hematologique. Leukemia 21: 121-128.
22. Cellot S, Krosl J, Chagraoui J, Meloche S, Humphries RK, Sauvageau G. (2007). Sustained in vitro trigger of self-renewal divisions in Hoxb4hiPbxl(10) hematopoietic stem cells. Exp Hematol 35: 802-816.
23. Chen F, Capecchi MR. (1997). Targeted mutations in hoxa-9 and hoxb-9 reveal synergistic interactions. Dev Biol 181: 186-196.
24. Chung KY, Morrone G, Schuringa JJ, Plasilova M, Shieh JH, Zhang Y et al. (2006). Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell proliferation. Cancer Res 66: 11781-11791.
25. Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL. (2003). Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 17: 3029-3035.
26. Crump JG, Swartz ME, Eberhart JK, Kimmel CB. (2006). Moz-dependent Hox expression controls segment-specific fate maps of skeletal precursors in the face. Development 133: 2661-2669.
27. Daser A, Rabbitts TH. (2005). The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis. Semin Cancer Biol 15: 175-188.
28. Davidson AJ, Ernst P, Wang Y, Dekens MP, Kingsley PD, Palis J et al. (2003). cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes. Nature 425: 300-306.
29. Davidson AJ, Zon LI. (2006). The caudal-related homeobox genes cdx1a and cdx4 act redundantly to regulate hox gene expression and the formation of putative hematopoietic stem cells during zebrafish embryogenesis. Dev Biol 292: 506-518.
30. De Braekeleer M, Morel F, Le Bris MJ, Herry A, Douet-Guilbert N. (2005). The MLL gene and translocations involving chromosomal band 11q23 in acute leukemia. Anticancer Res 25: 1931-1944.
31. Deshpande AJ, Cusan M, Rawat VP, Reuter H, Krause A, Pott C et al. (2006). Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia. Cancer Cell 10: 363-374.
32. Dik WA, Brahim W, Braun C, Asnafi V, Dastugue N, Bernard OA et al. (2005). CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes. Leukemia 19: 1948-1957.
33. DiMartino JF, Selleri L, Traver D, Firpo MT, Rhee J, Warnke R et al. (2001). The Hox cofactor and proto-oncogene Pbx1 is required for maintenance of definitive hematopoiesis in the fetal liver. Blood 98: 618-626.
34. Drabkin HA, Parsy C, Ferguson K, Guilhot F, Lacotte L, Roy L et al. (2002). Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia. Leukemia 16: 186-195.
35. Ekker SC, Jackson DG, von Kessler DP, Sun BI, Young KE, Beachy PA. (1994). The degree of variation in DNA sequence recognition among four Drosophila homeotic proteins. EMBO J 13: 3551-3560.
36. Ernst P, Mabon M, Davidson AJ, Zon LI, Korsmeyer SJ. (2004). An Mll-dependent Hox program drives hematopoietic progenitor expansion. Curr Biol 14: 2063-2069.
37. Ferrando AA, Armstrong SA, Neuberg DS, Sallan SE, Silverman LB, Korsmeyer SJ et al. (2003). Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation. Blood 102: 262-268.
38. Fine BM, Stanulla M, Schrappe M, Ho M, Viehmann S, Harbott J et al. (2004). Gene expression patterns associated with recurrent chromosomal translocations in acute lymphoblastic leukemia. Blood 103: 1043-1049.
39. Fischbach NA, Rozenfeld S, Shen W, Fong S, Chrobak D, Ginzinger D et al. (2005). 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 105: 1456-1466.
40. Fuller JF, McAdara J, Yaron Y, Sakaguchi M, Fraser JK, Gasson JC. (1999). Characterization of HOX gene expression during myelopoiesis: role of HOX A5 in lineage commitment and maturation. Blood 93: 3391-3400.
41. Gehring WJ, Affolter M, Burglin T. (1994). Homeodomain proteins. Annu Rev Biochem 63: 487-526.
42. Ghannam G, Takeda A, Camarata T, Moore MA, Viale A, Yaseen NR. (2004). The oncogene Nup98-HOXA9 induces gene transcription in myeloid cells. J Biol Chem 279: 866-875.
43. Giampaolo A, Pelosi E, Valtieri M, Montesoro E, Sterpetti P, Samoggia P et al. (1995). HOXB gene expression and function in differentiating purified hematopoietic progenitors. Stem Cells 13(Suppl 1): 90-105.
44. Giampaolo A, Sterpetti P, Bulgarini D, Samoggia P, Pelosi E, Valtieri M et al. (1994). Key functional role and lineage-specific expression of selected HOXB genes in purified hematopoietic progenitor differentiation. Blood 84: 3637-3647.
45. Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP et al. (1999). Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286: 531-537.
46. Greer JM, Puetz J, Thomas KR, Capecchi MR. (2000). Maintenance of functional equivalence during paralogous Hox gene evolution. Nature 403: 661-665.
47. Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR. (2005). The pathophysiology of HOX genes and their role in cancer. J Pathol 205: 154-171.
48. Hess JL, Bittner CB, Zeisig DT, Bach C, Fuchs U, Borkhardt A et al. (2006). c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells. Blood 108: 297-304.
49. Hisa T, Spence SE, Rachel RA, Fujita M, Nakamura T, Ward JM et al. (2004). Hematopoietic, angiogenic and eye defects in Meis1 mutant animals. EMBO J 23: 450-459.
50. Hoey T, Levine M. (1988). Divergent homeo box proteins recognize similar DNA sequences in Drosophila. Nature 332: 858-861.
51. Hope KJ, Jin L, Dick JE. (2004). Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5: 738-743.
52. Horan GS, Kovacs EN, Behringer RR, Featherstone MS. (1995a). Mutations in paralogous Hox genes result in overlapping homeotic transformations of the axial skeleton: evidence for unique and redundant function. Dev Biol 169: 359-372.
53. Horan GS, Ramirez-Solis R, Featherstone MS, Wolgemuth DJ, Bradley A, Behringer RR. (1995b). Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed. Genes Dev 9: 1667-1677.
54. Horton SJ, Grier DG, McGonigle GJ, Thompson A, Morrow M, De Silva I et al. (2005). Continuous MLL-ENL expression is necessary to establish a 'Hox Code' and maintain immortalization of hematopoietic progenitor cells. Cancer Res 65: 9245-9252.
55. Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N et al. (2004). MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6: 587-596.
56. Imamura T, Morimoto A, Takanashi M, Hibi S, Sugimoto T, Ishii E et al. (2002). Frequent co-expression of HoxA9 and Meis1 genes in infant acute lymphoblastic leukaemia with MLL rearrangement. Br J Haematol 119: 119-121.
57. Iwama A, Oguro H, Negishi M, Kato Y, Morita Y, Tsukui H et al. (2004). Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity 21: 843-851.
58. Iwasaki M, Kuwata T, Yamazaki Y, Jenkins NA, Copeland NG, Osato M et al. (2005). Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model. Blood 105: 784-793.
59. Izon DJ, Rozenfeld S, Fong ST, Komuves L, Largman C, Lawrence HJ. (1998). Loss of function of the homeobox gene Hoxa-9 perturbs early T-cell development and induces apoptosis in primitive thymocytes. Blood 92: 383-393.
60. Jacobs JJ, Kieboom K, Marino S, DePinho RA, van Lohuizen M. (1999). The oncogene and polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397: 164-168.
61. Jin G, Yamazaki Y, Takuwa M, Takahara T, Kaneko K, Kuwata T et al. (2007). Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis. Blood 109: 3998-4005.
62. Kappen C. (2000). Disruption of the homeobox gene Hoxb-6 in mice results in increased numbers of early erythrocyte progenitors. Am J Hematol 65: 111-118.
63. Kasper LH, Brindle PK, Schnabel CA, Pritchard CE, Cleary ML, van Deursen JM. (1999). CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity. Mol Cell Biol 19: 764-776.
64. Kato Y, Iwama A, Tadokoro Y, Shimoda K, Minoguchi M, Akira S et al. (2005). Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis. J Exp Med 202: 169-179.
65. Kawagoe H, Humphries RK, Blair A, Sutherland HJ, Hogge DE. (1999). Expression of HOX genes, HOX cofactors, and MLL in phenotypically and functionally defined subpopulations of leukemic and normal human hematopoietic cells. Leukemia 13: 687-698.
66. Ko KH, Lam QL, Zhang M, Wong CK, Lo CK, Kahmeyer-Gabbe M et al. (2007). Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow. Exp Hematol 35: 465-475.
67. Kohlmann A, Schoch C, Schnittger S, Dugas M, Hiddemann W, Kern W et al. (2003). Molecular characterization of acute leukemias by use of microarray technology. Genes Chromosomes Cancer 37: 396-405.
68. Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J et al. (2006). Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442: 818-822.
69. Kroon E, Krosl J, Thorsteinsdottir U, Baban S, Buchberg AM, Sauvageau G. (1998). Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b. EMBO J 17: 3714-3725.
70. Kroon E, Thorsteinsdottir U, Mayotte N, Nakamura T, Sauvageau G. (2001). NUP98-HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice. EMBO J 20: 350-361.
71. Krosl J, Beslu N, Mayotte N, Humphries RK, Sauvageau G. (2003). The competitive nature of HOXB4-transduced HSC is limited by PBX1: the generation of ultra-competitive stem cells retaining full differentiation potential. Immunity 18: 561-571.
72. Krumlauf R. (1994). Hox genes in vertebrate development. Cell 78: 191-201.
73. Kumar AR, Hudson WA, Chen W, Nishiuchi R, Yao Q, Kersey JH. (2004). Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia. Blood 103: 1823-1828.
74. Lam DH, Aplan PD. (2001). NUP98 gene fusions in hematologic malignancies. Leukemia 15: 1689-1695.
75. Lawrence HJ, Christensen J, Fong S, Hu YL, Weissman I, Sauvageau G et al. (2005). Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells. Blood 106: 3988-3994.
76. Lawrence HJ, Helgason CD, Sauvageau G, Fong S, Izon DJ, Humphries RK et al. (1997). Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis. Blood 89: 1922-1930.
77. Lawrence HJ, Rozenfeld S, Cruz C, Matsukuma K, Kwong A, Komuves L et al. (1999). Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias. Leukemia 13: 1993-1999.
78. Lawrence HJ, Sauvageau G, Humphries RK, Largman C. (1996). The role of HOX homeobox genes in normal and leukemic hematopoiesis. Stem Cells 14: 281-291.
79. Lessard J, Sauvageau G. (2003). Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423: 255-260.
80. Lin YW, Slape C, Zhang Z, Aplan PD. (2005). NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia. Blood 106: 287-295.
81. Mamo A, Krosl J, Kroon E, Bijl J, Thompson A, Mayotte N et al. (2006). Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation. Blood 108: 622-629.
82. Mann RS. (1995). The specificity of homeotic gene function. BioEssays 17: 855-863.
83. Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y et al. (2004). Characterization of clonogenic multiple myeloma cells. Blood 103: 2332-2336.
84. Miller CT, Maves L, Kimmel CB. (2004). moz regulates Hox expression and pharyngeal segmental identity in zebrafish. Development 131: 2443-2461.
85. Miyamoto T, Weissman IL, Akashi K. (2000). AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 97: 7521-7526.
86. Moens CB, Selleri L. (2006). Hox cofactors in vertebrate development. Dev Biol 291: 193-206.
87. Moretti P, Simmons P, Thomas P, Haylock D, Rathjen P, Vadas M et al. (1994). Identification of homeobox genes expressed in human haemopoietic progenitor cells. Gene 144: 213-219.
88. Morgado E, Albouhair S, Lavau C. (2007). Flt3is dispensable to the Hoxa9/Meis1 leukemogenic cooperation. Blood 109: 4020-4022.
89. Moskow JJ, Bullrich F, Huebner K, Daar IO, Buchberg AM. (1995). Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice. Mol Cell Biol 15: 5434-5443.
90. Nakamura T. (2005). NUP98 fusion in human leukemia: dysregulation of the nuclear pore and homeodomain proteins. Int J Hematol 82: 21-27.
91. O'Brien CA, Pollett A, Gallinger S, Dick JE. (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445: 106-110.
92. Ohta H, Sekulovic S, Bakovic S, Eaves CJ, Pineault N, Gasparetto M et al. (2007). Near maximal-expansions of hematopoietic stem cells in culture using NUP98-HOX fusions. Exp Hematol 35: 817-830.
93. Okada Y, Jiang Q, Lemieux M, Jeannotte L, Su L, Zhang Y. (2006). Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L. Nat Cell Biol 8: 1017-1024.
94. Owens BM, Hawley RG. (2002). HOX and non-HOX homeobox genes in leukemic hematopoiesis. Stem Cells 20: 364-379.
95. Ozeki K, Kiyoi H, Hirose Y, Iwai M, Ninomiya M, Kodera Y et al. (2004). Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia. Blood 103: 1901-1908.
96. Palmqvist L, Argiropoulos B, Pineault N, Abramovich C, Sly LM, Krystal G et al. (2006). The Flt3receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia. Blood 108: 1030-1036.
97. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL et al. (2003). Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423: 302-305.
98. Passegue E, Wagner EF, Weissman IL. (2004). JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells. Cell 119: 431-443.
99. Pineault N, Abramovich C, Humphries RK. (2005). Transplantable cell lines generated with NUP98-Hox fusion genes undergo leukemic progression by Meis1 independent of its binding to DNA. Leukemia 19: 636-643.
100. Pineault N, Abramovich C, Ohta H, Humphries RK. (2004). Differential and common leukemogenic potentials of multiple NUP98-Hox fusion proteins alone or with Meis1. Mol Cell Biol 24: 1907-1917.
101. Pineault N, Buske C, Feuring-Buske M, Abramovich C, Rosten P, Hogge DE et al. (2003). Induction of acute myeloid leukemia in mice by the human leukemia-specific fusion gene NUP98-HOXD13 in concert with Meis1. Blood 101: 4529-4538.
102. Pineault N, Helgason CD, Lawrence HJ, Humphries RK. (2002). Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny. Exp Hematol 30: 49-57.
103. Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D et al. (2005). Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65: 5506-5511.
104. Quentmeier H, Dirks WG, Macleod RA, Reinhardt J, Zaborski M, Drexler HG. (2004). Expression of HOX genes in acute leukemia cell lines with and without MLL translocations. Leuk Lymphoma 45: 567-574.
105. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K et al. (2003). A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423: 409-414.
106. Rozovskaia T, Feinstein E, Mor O, Foa R, Blechman J, Nakamura T et al. (2001). Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4:11) abnormality. Oncogene 20: 874-878.
107. Satoh Y, Matsumura I, Tanaka H, Ezoe S, Sugahara H, Mizuki M et al. (2004). Roles for c-Myc in self-renewal of hematopoietic stem cells. J Biol Chem 279: 24986-24993.
108. Sauvageau G, Lansdorp PM, Eaves CJ, Hogge DE, Dragowska WH, Reid DS et al. (1994). Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc Natl Acad Sci USA 91: 12223-12227.
109. Sauvageau G, Thorsteinsdottir U, Eaves CJ, Lawrence HJ, Largman C, Lansdorp PM et al. (1995). Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev 9: 1753-1765.
110. Sauvageau G, Thorsteinsdottir U, Hough MR, Hugo P, Lawrence HJ, Largman C et al. (1997). Overexpression of HOXB3in hematopoietic cells causes defective lymphoid development and progressive myeloproliferation. Immunity 6: 13-22.
111. Schreiner S, Birke M, Garcia-Cuellar MP, Zilles O, Greil J, Slany RK. (2001). MLL-ENL causes a reversible and myc-dependent block of myelomonocytic cell differentiation. Cancer Res 61: 6480-6486.
112. Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G. (2007). Genome regulation by polycomb and trithorax proteins. Cell 128: 735-745.
113. Shen WF, Detmer K, Mathews CH, Hack FM, Morgan DA, Largman C et al. (1992). Modulation of homeobox gene expression alters the phenotype of human hematopoietic cell lines. EMBO J 11: 983-989.
114. Shen WF, Montgomery JC, Rozenfeld S, Moskow JJ, Lawrence HJ, Buchberg AM et al. (1997). AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins. Mol Cell Biol 17: 6448-6458.
115. Shimamoto T, Tang Y, Naot Y, Nardi M, Brulet P, Bieberich CJ et al. (1999). Hematopoietic progenitor cell abnormalities in Hoxc-8 null mutant mice. J Exp Zool 283: 186-193.
116. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al. (2004). Identification of human brain tumour initiating cells. Nature 432: 396-401.
117. Slape C, Aplan PD. (2004). The role of NUP98 gene fusions in hematologic malignancy. Leuk Lymphoma 45: 1341-1350.
118. So CW, Karsunky H, Wong P, Weissman IL, Cleary ML. (2004). Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. Blood 103: 3192-3199.
119. Somervaille TC, Cleary ML. (2006). Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia. Cancer Cell 10: 257-268.
120. Soulier J, Clappier E, Cayuela JM, Regnault A, Garcia-Peydro M, Dombret H et al. (2005). HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). Blood 106: 274-286.
121. Speleman F, Cauwelier B, Dastugue N, Cools J, Verhasselt B, Poppe B et al. (2005). A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. Leukemia 19: 358-366.
122. Suemori H, Noguchi S. (2000). Hox C cluster genes are dispensable for overall body plan of mouse embryonic development. Dev Biol 220: 333-342.
123. Taussig DC, Pearce DJ, Simpson C, Rohatiner AZ, Lister TA, Kelly G et al. (2005). Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood 106: 4086-4092.
124. Thorsteinsdottir U, Kroon E, Jerome L, Blasi F, Sauvageau G. (2001). Defining roles for HOX and MEIS1 genes in induction of acute myeloid leukemia. Mol Cell Biol 21: 224-234.
125. Thorsteinsdottir U, Mamo A, Kroon E, Jerome L, Bijl J, Lawrence HJ et al. (2002). Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood 99: 121-129.
126. Thorsteinsdottir U, Sauvageau G, Hough MR, Dragowska W, Lansdorp PM, Lawrence HJ et al. (1997). Overexpression of HOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia. Mol Cell Biol 17: 495-505.
127. Thorsteinsdottir U, Sauvageau G, Humphries RK. (1999). Enhanced in vivo regenerative potential of HOXB4-transduced hematopoietic stem cells with regulation of their pool size. Blood 94: 2605-2612.
128. Tsutsumi S, Taketani T, Nishimura K, Ge X, Taki T, Sugita K et al. (2003). Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements. Cancer Res 63: 4882-4887.
129. Tupler R, Perini G, Green MR. (2001). Expressing the human genome. Nature 409: 832-833.
130. Uchida N, Dykstra B, Lyons KJ, Leung FY, Eaves CJ. (2003). Different in vivo repopulating activities of purified hematopoietic stem cells before and after being stimulated to divide in vitro with the same kinetics. Exp Hematol 31: 1338-1347.
131. van der Lugt NM, Alkema M, Berns A, Deschamps J. (1996). The polycomb-group homolog Bmi-1 is a regulator of murine Hox gene expression. Mech Dev 58: 153-164.
132. Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S et al. (2000). Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med 6: 1278-1281.
133. Wang GG, Pasillas MP, Kamps MP. (2005). Meis1 programs transcription of FLT3 and cancer stem cell character, using a mechanism that requires interaction with Pbx and a novel function of the Meis1 C-terminus. Blood 106: 254-264.
134. Wang GG, Pasillas MP, Kamps MP. (2006). Persistent transactivation by meis1 replaces hox function in myeloid leukemogenesis models: evidence for co-occupancy of meis1-pbx and hox-pbx complexes on promoters of leukemia-associated genes. Mol Cell Biol 26: 3902-3916.
135. Xin L, Lawson DA, Witte ON. (2005). The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc Natl Acad Sci USA 102: 6942-6947.
136. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R et al. (2002). Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1: 133-143.
137. Zakany J, Fromental-Ramain C, Warot X, Duboule D. (1997). Regulation of number and size of digits by posterior Hox genes: a dose-dependent mechanism with potential evolutionary implications. Proc Natl Acad Sci USA 94: 13695-13700.
138. Zakany J, Gerard M, Favier B, Potter SS, Duboule D. (1996). Functional equivalence and rescue among group 11 Hox gene products in vertebral patterning. Dev Biol 176: 325-328.
139. Zeisig BB, Milne T, Garcia-Cuellar MP, Schreiner S, Martin ME, Fuchs U et al. (2004). Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol 24: 617-628.
140. Zhang XB, Beard BC, Beebe K, Storer B, Humphries RK, Kiem HP. (2006). Differential effects of HOXB4 on nonhuman primate short- and long-term repopulating cells. PLoS Med 3: e173.