| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CONCISE REVIEW |
a Veterans Affairs Medical Center, University of California, Department of Medicine, San Francisco, California, USA;
b Clinical Research Institute of Montreal, Montreal, Quebec, Canada;
c Terry Fox Laboratory, British Columbia Cancer Agency, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Key Words. Homeobox genes • Hematopoiesis • Transcription factors • Transgenic mice • Stem cells • Leukemia
Dr. Corey Largman, Hematopoiesis Research (151H), Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
A sizable amount of new data points to a role for the HOX family of homeobox genes in hematopoiesis. Recent studies have demonstrated that HOXA and HOXB genes are expressed in human CD34+ cells, and are downregulated as cells leave the CD34+ compartment. In addition, expression of certain genes, including HOXB3 and HOXB4, is largely restricted to the long-term culture-initiating cell enriched pool, containing the putative stem cell population. Studies have also shown that HOX genes appear to be important for normal T lymphocyte and activated natural killer cell function. Overexpression of Hox-b4 in transplanted murine marrow cells results in a dramatic expansion of stem cells, while maintaining normal peripheral blood counts. In contrast, overexpression of Hox-a10 resulted in expansion of progenitor pools, accompanied by unique changes in the differentiation patterns of committed progenitors. Overexpression of Hox-a10 or Hox-b8 led to the development of myeloid leukemias, while animals transfected with marrow cells overexpressing Hox-b4 do not appear to develop malignancies. Blockade of HOX gene function using antisense oligonucleotides has revealed that several HOX genes appear to influence either myeloid or erythroid colony formation. Mice homozygous for a targeted disruption of the Hox-a9 gene show reduced numbers of granulocytes and lymphocytes, smaller spleens and thymuses, and reduced numbers of committed progenitors. These studies demonstrate that HOX homeobox genes play a role in both the early stem cell function as well as in later stages of hematopoietic differentiation, and that perturbations of HOX gene expression can be leukemogenic.
This article has been cited by other articles:
|
|
 |
|
  B. Ruhin-Poncet, S. Ghoul-Mazgar, D. Hotton, F. Capron, M. H. Jaafoura, G. Goubin, and A. Berdal Msx and Dlx Homeogene Expression in Epithelial Odontogenic Tumors J. Histochem. Cytochem., January 1, 2009; 57(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bandyopadhyay, M. Z. Ashraf, P. Daher, P. H. Howe, and P. E. DiCorleto HOXA9 Participates in the Transcriptional Activation of E-Selectin in Endothelial Cells Mol. Cell. Biol., June 15, 2007; 27(12): 4207 - 4216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Magnusson, A. C. M. Brun, N. Miyake, J. Larsson, M. Ehinger, J. M. Bjornsson, A. Wutz, M. Sigvardsson, and S. Karlsson HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development Blood, May 1, 2007; 109(9): 3687 - 3696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Lensch and G. Q. Daley Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells Blood, April 1, 2006; 107(7): 2605 - 2612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Olsen, D. L. Stachura, and M. J. Weiss Designer blood: creating hematopoietic lineages from embryonic stem cells Blood, February 15, 2006; 107(4): 1265 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, F. Yates, O. Naveiras, P. Ernst, and G. Q. Daley Embryonic stem cell-derived hematopoietic stem cells PNAS, December 27, 2005; 102(52): 19081 - 19086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Lawrence, J. Christensen, S. Fong, Y.-L. Hu, I. Weissman, G. Sauvageau, R. K. Humphries, and C. Largman Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells Blood, December 1, 2005; 106(12): 3988 - 3994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Soulier, E. Clappier, J.-M. Cayuela, A. Regnault, M. Garcia-Peydro, H. Dombret, A. Baruchel, M.-L. Toribio, and F. Sigaux HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL) Blood, July 1, 2005; 106(1): 274 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Fischbach, S. Rozenfeld, W. Shen, S. Fong, D. Chrobak, D. Ginzinger, S. C. Kogan, A. Radhakrishnan, M. M. Le Beau, C. Largman, 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, February 15, 2005; 105(4): 1456 - 1466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Vijapurkar, N. Fischbach, W. Shen, C. Brandts, D. Stokoe, H. J. Lawrence, and C. Largman Protein Kinase C-Mediated Phosphorylation of the Leukemia-Associated HOXA9 Protein Impairs Its DNA Binding Ability and Induces Myeloid Differentiation Mol. Cell. Biol., May 1, 2004; 24(9): 3827 - 3837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Daser and T. H. Rabbitts Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis Genes & Dev., May 1, 2004; 18(9): 965 - 974. [Full Text] [PDF]
|
|
|
|
|
|
S. T. Dorsam, C. M. Ferrell, G. P. Dorsam, M. K. Derynck, U. Vijapurkar, D. Khodabakhsh, B. Pau, H. Bernstein, C. M. Haqq, C. Largman, et al. The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells Blood, March 1, 2004; 103(5): 1676 - 1684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ghannam, A. Takeda, T. Camarata, M. A. Moore, A. Viale, and N. R. Yaseen The Oncogene Nup98-HOXA9 Induces Gene Transcription in Myeloid Cells J. Biol. Chem., January 9, 2004; 279(2): 866 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cozzio, E. Passegue, P. M. Ayton, H. Karsunky, M. L. Cleary, and I. L. Weissman Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors Genes & Dev., December 15, 2003; 17(24): 3029 - 3035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Guo, R. Chan, H. Ramsey, W. Li, X. Xie, W. C. Shelley, J. P. Martinez-Barbera, B. Bort, K. Zaret, M. Yoder, et al. The homeoprotein Hex is required for hemangioblast differentiation Blood, October 1, 2003; 102(7): 2428 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. LaRonde-LeBlanc and C. Wolberger Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior Genes & Dev., August 15, 2003; 17(16): 2060 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Okada, R. Nagai, T. Sato, E. Matsuura, T. Minami, I. Morita, and T. Doi Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene Blood, June 15, 2003; 101(12): 4748 - 4756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Saeki, K. Saeki, and A. Yuo Distinct involvement of cAMP-response element-dependent transcriptions in functional and morphological maturation during retinoid-mediated human myeloid differentiation J. Leukoc. Biol., May 1, 2003; 73(5): 673 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Thompson, M. F. Quinn, D. Grimwade, C. M. O'Neill, M. R. Ahmed, S. Grimes, M. F. McMullin, F. Cotter, and T. R. J. Lappin Global down-regulation of HOX gene expression in PML-RARalpha + acute promyelocytic leukemia identified by small-array real-time PCR Blood, February 15, 2003; 101(4): 1558 - 1565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Collins, A. Appert, L. Ariza-McNaughton, R. Pannell, Y. Yamada, and T. H. Rabbitts Mouse Af9 Is a Controller of Embryo Patterning, Like Mll, Whose Human Homologue Fuses with AF9 after Chromosomal Translocation in Leukemia Mol. Cell. Biol., October 15, 2002; 22(20): 7313 - 7324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. C. Haznedaroglu, H. Goker, M. Turgut, Y. Buyukasik, and M. Benekli Thrombopoietin as a Drug: Biologic Expectations, Clinical Realities, and Future Directions Clinical and Applied Thrombosis/Hemostasis, July 1, 2002; 8(3): 193 - 212. [Abstract] [PDF]
|
|
|
|
|
|
T. Taghon, F. Stolz, M. De Smedt, M. Cnockaert, B. Verhasselt, J. Plum, and G. Leclercq HOX-A10 regulates hematopoietic lineage commitment: evidence for a monocyte-specific transcription factor Blood, February 15, 2002; 99(4): 1197 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Fujino, A. Suzuki, Y. Ito, K. Ohyashiki, Y. Hatano, I. Miura, and T. Nakamura 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) Blood, February 15, 2002; 99(4): 1428 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kastner, H. J. Lawrence, C. Waltzinger, N. B. Ghyselinck, P. Chambon, and S. Chan Positive and negative regulation of granulopoiesis by endogenous RAR{alpha} Blood, March 1, 2001; 97(5): 1314 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Giannola, W. D. Shlomchik, M. Jegathesan, D. Liebowitz, C. S. Abrams, T. Kadesch, A. Dancis, and S. G. Emerson Hematopoietic Expression of HOXB4 Is Regulated in Normal and Leukemic Stem Cells through Transcriptional Activation of the HOXB4 Promoter by Upstream Stimulating Factor (USF)-1 and USF-2 J. Exp. Med., November 20, 2000; 192(10): 1479 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Calvo, D. B. Sykes, M. Pasillas, and M. P. Kamps 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., May 1, 2000; 20(9): 3274 - 3285. [Abstract] [Full Text]
|
|
|
|
 |
|
 C Winchester, S Robertson, T MacLeod, K Johnson, and M Thomas Expression of a homeobox gene (SIX5) in borderline ovarian tumours J. Clin. Pathol., March 1, 2000; 53(3): 212 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Thorsteinsdottir, G. Sauvageau, and R. K. Humphries Enhanced In Vivo Regenerative Potential of HOXB4-Transduced Hematopoietic Stem Cells With Regulation of Their Pool Size Blood, October 15, 1999; 94(8): 2605 - 2612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Thorsteinsdottir, J. Krosl, E. Kroon, A. Haman, T. Hoang, and G. Sauvageau The Oncoprotein E2A-Pbx1a Collaborates with Hoxa9 To Acutely Transform Primary Bone Marrow Cells Mol. Cell. Biol., September 1, 1999; 19(9): 6355 - 6366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakamura, Y. Yamazaki, Y. Hatano, and I. Miura NUP98 Is Fused to PMX1 Homeobox Gene in Human Acute Myelogenous Leukemia With Chromosome Translocation t(1;11)(q23;p15) Blood, July 15, 1999; 94(2): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-F. Shen, S. Rozenfeld, A. Kwong, L. G. Komuves, H. J. Lawrence, and C. Largman HOXA9 Forms Triple Complexes with PBX2 and MEIS1 in Myeloid Cells Mol. Cell. Biol., April 1, 1999; 19(4): 3051 - 3061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Hough, M. D. Reis, R. Singaraja, D. M. Bryce, S. Kamel-Reid, I. Dardick, M. L. Breitman, and I. D. Dube A model for spontaneous B-lineage lymphomas in IgHµ-HOX11 transgenic mice PNAS, November 10, 1998; 95(23): 13853 - 13858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Ford, E. N. Kabingu, E. A. Bump, G. L. Mutter, and A. B. Pardee Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: A possible mechanism of breast carcinogenesis PNAS, October 13, 1998; 95(21): 12608 - 12613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Brummendorf, W. Dragowska, J.M. J.M. Zijlmans, G. Thornbury, and P. M. Lansdorp Asymmetric Cell Divisions Sustain Long-Term Hematopoiesis from Single-sorted Human Fetal Liver Cells J. Exp. Med., September 21, 1998; 188(6): 1117 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Izon, S. Rozenfeld, S. T. Fong, L. Komuves, C. Largman, and H. J. Lawrence Loss of Function of the Homeobox Gene Hoxa-9 Perturbs Early T-Cell Development and Induces Apoptosis in Primitive Thymocytes Blood, July 15, 1998; 92(2): 383 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Green, I. Rambaldi, J. Teakles, and M. S. Featherstone A Conserved C-terminal Domain in PBX Increases DNA Binding by the PBX Homeodomain and Is Not a Primary Site of Contact for the YPWM Motif of HOXA1 J. Biol. Chem., May 22, 1998; 273(21): 13273 - 13279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Godwin and M. R. Capecchi Hoxc13 mutant mice lack external hair Genes & Dev., January 1, 1998; 12(1): 11 - 20. [Abstract] [Full Text]
|
|
|
|
|
|
J. R. Gruen and S. M. Weissman Evolving Views of the Major Histocompatibility Complex Blood, December 1, 1997; 90(11): 4252 - 4265. [Full Text] [PDF]
|
|
|
|
|
|
J. J. Bijl, J. W. van Oostveen, J. M.M. Walboomers, A. Horstman, A. J.C. van den Brule, R. Willemze, and C. J.L.M. Meijer HOXC4, HOXC5, and HOXC6 Expression in Non-Hodgkin's Lymphoma: Preferential Expression of the HOXC5 Gene in Primary Cutaneous Anaplastic T-Cell and Oro-Gastrointestinal Tract Mucosa-Associated B-Cell Lymphomas Blood, November 15, 1997; 90(10): 4116 - 4125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Tenen, R. Hromas, J. D. Licht, and D.-E. Zhang Transcription Factors, Normal Myeloid Development, and Leukemia Blood, July 15, 1997; 90(2): 489 - 519. [Full Text] [PDF]
|
|
|
|
|
|
H. J. Lawrence, C. D. Helgason, G. Sauvageau, S. Fong, D. J. Izon, R. K. Humphries, and C. Largman Mice Bearing a Targeted Interruption of the Homeobox Gene HOXA9 Have Defects in Myeloid, Erythroid, and Lymphoid Hematopoiesis Blood, March 15, 1997; 89(6): 1922 - 1930. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| STEM CELLS | THE ONCOLOGIST | CME | ALPHAMED PRESS JOURNALS |
