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Gene Review

HOXA9  -  homeobox A9

Homo sapiens

Synonyms: ABD-B, HOX1, HOX1.7, HOX1G, Homeobox protein Hox-1G, ...
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Disease relevance of HOXA9


High impact information on HOXA9

  • Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia [6].
  • These studies identify HOXA9 as an important human myeloid leukaemia gene and suggest an important role for nucleoporins in human myeloid leukaemia given that a second nucleoporin, NUP214, has also been implicated in human myeloid leukaemia [6].
  • Chimaeric messages spliced over the breakpoint fuse the GLFG repeat domains of NUP98 in-frame to the HOXA9 homeobox [7].
  • The predicted NUP98-HOXA9 fusion protein may promote leukaemogenesis through inhibition of HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport [7].
  • Moreover, Hoxa7 and Hoxa9 were specifically required for efficient in vitro myeloid immortalization by an MLL fusion protein but not other leukemogenic fusion proteins [8].

Biological context of HOXA9


Anatomical context of HOXA9


Associations of HOXA9 with chemical compounds

  • In human uterine or cervical cell cultures, DES induces HOXA9 or HOXA10 gene expression, respectively, to levels approximately twofold that induced by estradiol [15].
  • This case fits with and extends a recently proposed multistage AML model in which constitutive activation of tyrosine kinases by mutations (BCR-ABL1) are associated with deregulation of transcription factors central to myeloid differentiation (HOXA9 secondary to PICALM-MLLT10) [16].
  • METHODS AND FINDINGS: Here, we show that the expression level of Hoxa9 is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3) [17].
  • We now report that six different genes of the cluster HOX 1 are sequentially induced by RA in a similar temporal pattern, beginning with genes at the 3' end of the cluster [18].

Physical interactions of HOXA9

  • Taken together, these data suggest that in myeloid leukemia cells MEIS1 forms trimeric complexes with PBX and HOXA9, which in turn can bind to consensus PBX-HOXA9 DNA targets [2].
  • Here we demonstrate that the NUP98-HOXA9 fusion gene encodes two nuclear oncoproteins with either 19 or 37 NUP98 FG repeats fused to the DNA binding and PBX heterodimerization domains of the transcription factor HOXA9 [19].
  • Smad4 interacts directly with the homeodomain of Hoxa9 and blocks the ability of Nup98-Hoxa9 to bind DNA, thereby suppressing its ability to regulate downstream gene transcription [20].
  • Also, we found that both Hoxc-8 and Hoxa-9 bound to a Hox binding site adjacent to Smad3 binding sequence [21].
  • We show that HOXA9 protein binds to the Pim1 promoter and induces Pim1 mRNA and protein in hematopoietic cells [22].

Regulatory relationships of HOXA9


Other interactions of HOXA9


Analytical, diagnostic and therapeutic context of HOXA9


  1. Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model. Iwasaki, M., Kuwata, T., Yamazaki, Y., Jenkins, N.A., Copeland, N.G., Osato, M., Ito, Y., Kroon, E., Sauvageau, G., Nakamura, T. Blood (2005) [Pubmed]
  2. HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells. Shen, W.F., Rozenfeld, S., Kwong, A., Köm ves, L.G., Lawrence, H.J., Largman, C. Mol. Cell. Biol. (1999) [Pubmed]
  3. A novel gene, MSI2, encoding a putative RNA-binding protein is recurrently rearranged at disease progression of chronic myeloid leukemia and forms a fusion gene with HOXA9 as a result of the cryptic t(7;17)(p15;q23). Barbouti, A., Höglund, M., Johansson, B., Lassen, C., Nilsson, P.G., Hagemeijer, A., Mitelman, F., Fioretos, T. Cancer Res. (2003) [Pubmed]
  4. Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell proliferation. Chung, K.Y., Morrone, G., Schuringa, J.J., Plasilova, M., Shieh, J.H., Zhang, Y., Zhou, P., Moore, M.A. Cancer Res. (2006) [Pubmed]
  5. A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Dash, A.B., Williams, I.R., Kutok, J.L., Tomasson, M.H., Anastasiadou, E., Lindahl, K., Li, S., Van Etten, R.A., Borrow, J., Housman, D., Druker, B., Gilliland, D.G. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nakamura, T., Largaespada, D.A., Lee, M.P., Johnson, L.A., Ohyashiki, K., Toyama, K., Chen, S.J., Willman, C.L., Chen, I.M., Feinberg, A.P., Jenkins, N.A., Copeland, N.G., Shaughnessy, J.D. Nat. Genet. (1996) [Pubmed]
  7. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Borrow, J., Shearman, A.M., Stanton, V.P., Becher, R., Collins, T., Williams, A.J., Dubé, I., Katz, F., Kwong, Y.L., Morris, C., Ohyashiki, K., Toyama, K., Rowley, J., Housman, D.E. Nat. Genet. (1996) [Pubmed]
  8. Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9. Ayton, P.M., Cleary, M.L. Genes Dev. (2003) [Pubmed]
  9. Thrombopoietin induces HOXA9 nuclear transport in immature hematopoietic cells: potential mechanism by which the hormone favorably affects hematopoietic stem cells. Kirito, K., Fox, N., Kaushansky, K. Mol. Cell. Biol. (2004) [Pubmed]
  10. Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells. Fiskus, W., Pranpat, M., Balasis, M., Herger, B., Rao, R., Chinnaiyan, A., Atadja, P., Bhalla, K. Mol. Cancer Ther. (2006) [Pubmed]
  11. Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis. Lawrence, H.J., Helgason, C.D., Sauvageau, G., Fong, S., Izon, D.J., Humphries, R.K., Largman, C. Blood (1997) [Pubmed]
  12. The oncogene Nup98-HOXA9 induces gene transcription in myeloid cells. Ghannam, G., Takeda, A., Camarata, T., Moore, M.A., Viale, A., Yaseen, N.R. J. Biol. Chem. (2004) [Pubmed]
  13. Aberrant expression of HOXA9, DEK, CBL and CSF1R in acute myeloid leukemia. Casas, S., Nagy, B., Elonen, E., Aventín, A., Larramendy, M.L., Sierra, J., Ruutu, T., Knuutila, S. Leuk. Lymphoma (2003) [Pubmed]
  14. Expression of HOX genes in acute leukemia cell lines with and without MLL translocations. Quentmeier, H., Dirks, W.G., Macleod, R.A., Reinhardt, J., Zaborski, M., Drexler, H.G. Leuk. Lymphoma (2004) [Pubmed]
  15. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing müllerian system. Block, K., Kardana, A., Igarashi, P., Taylor, H.S. FASEB J. (2000) [Pubmed]
  16. Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9. Sindt, A., Deau, B., Brahim, W., Staal, A., Visanica, S., Villarese, P., Rault, J.P., Macintyre, E., Delabesse, E. Genes Chromosomes Cancer (2006) [Pubmed]
  17. Cdx4 and menin co-regulate hoxa9 expression in hematopoietic cells. Yan, J., Chen, Y.X., Desmond, A., Silva, A., Yang, Y., Wang, H., Hua, X. PLoS ONE (2006) [Pubmed]
  18. Alteration of homeobox gene expression by N-ras transformation of PA-1 human teratocarcinoma cells. Buettner, R., Yim, S.O., Hong, Y.S., Boncinelli, E., Tainsky, M.A. Mol. Cell. Biol. (1991) [Pubmed]
  19. CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity. Kasper, L.H., Brindle, P.K., Schnabel, C.A., Pritchard, C.E., Cleary, M.L., van Deursen, J.M. Mol. Cell. Biol. (1999) [Pubmed]
  20. TGFbeta/BMP inhibits the bone marrow transformation capability of Hoxa9 by repressing its DNA-binding ability. Wang, N., Kim, H.G., Cotta, C.V., Wan, M., Tang, Y., Klug, C.A., Cao, X. EMBO J. (2006) [Pubmed]
  21. Hoxa-9 represses transforming growth factor-beta-induced osteopontin gene transcription. Shi, X., Bai, S., Li, L., Cao, X. J. Biol. Chem. (2001) [Pubmed]
  22. Evidence that the Pim1 kinase gene is a direct target of HOXA9. Hu, Y.L., Passegué, E., Fong, S., Largman, C., Lawrence, H.J. Blood (2007) [Pubmed]
  23. Synergistic action of MLL, a TRX protein with template activating factor-I, a histone chaperone. Shimoyama, T., Kato, K., Miyaji-Yamaguchi, M., Nagata, K. FEBS Lett. (2005) [Pubmed]
  24. MEIS1 and HOXA7 genes in human acute myeloid leukemia. Afonja, O., Smith, J.E., Cheng, D.M., Goldenberg, A.S., Amorosi, E., Shimamoto, T., Nakamura, S., Ohyashiki, K., Ohyashiki, J., Toyama, K., Takeshita, K. Leuk. Res. (2000) [Pubmed]
  25. Tumor suppressor p16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells. Reynolds, P.A., Sigaroudinia, M., Zardo, G., Wilson, M.B., Benton, G.M., Miller, C.J., Hong, C., Fridlyand, J., Costello, J.F., Tlsty, T.D. J. Biol. Chem. (2006) [Pubmed]
  26. Eukaryotic translation initiation factor 4E activity is modulated by HOXA9 at multiple levels. Topisirovic, I., Kentsis, A., Perez, J.M., Guzman, M.L., Jordan, C.T., Borden, K.L. Mol. Cell. Biol. (2005) [Pubmed]
  27. HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo. Fischbach, N.A., Rozenfeld, S., Shen, W., Fong, S., Chrobak, D., Ginzinger, D., Kogan, S.C., Radhakrishnan, A., Le Beau, M.M., Largman, C., Lawrence, H.J. Blood (2005) [Pubmed]
  28. HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells. Bandyopadhyay, S., Ashraf, M.Z., Daher, P., Howe, P.H., DiCorleto, P.E. Mol. Cell. Biol. (2007) [Pubmed]
  29. Single-translocation and double-chimeric transcripts: detection of NUP98-HOXA9 in myeloid leukemias with HOXA11 or HOXA13 breaks of the chromosomal translocation t(7;11)(p15;p15). Fujino, T., Suzuki, A., Ito, Y., Ohyashiki, K., Hatano, Y., Miura, I., Nakamura, T. Blood (2002) [Pubmed]
  30. Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias. Lawrence, H.J., Rozenfeld, S., Cruz, C., Matsukuma, K., Kwong, A., Kömüves, L., Buchberg, A.M., Largman, C. Leukemia (1999) [Pubmed]
  31. A case of acute myeloid leukemia with t(7;11)(p15;p15) mimicking myeloid crisis of chronic myelogenous leukemia. Kawakami, K., Miyanishi, S., Nishii, K., Usui, E., Murata, T., Shinsato, I., Shiku, H. Int. J. Hematol. (2002) [Pubmed]
  32. Low frequency of rearrangements of the homeobox gene HOXA9/t(7;11) in adult acute myeloid leukemia. Kwong, Y.L., Pang, A. Genes Chromosomes Cancer (1999) [Pubmed]
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