SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on January 23, 2003; DOI 10.1182/blood-2002-08-2484. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2484v1 101/11/4529    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pineault, N. Articles by Humphries, R. K. Search for Related Content PubMed PubMed Citation Articles by Pineault, N. Articles by Humphries, R. K. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4529-4538 NEOPLASIA Induction of acute myeloid leukemia in mice by the human leukemia-specific fusion gene NUP98-HOXD13 in concert with Meis1 Nicolas Pineault, Christian Buske, Michaela Feuring-Buske, Carolina Abramovich, Patty Rosten, Donna E. Hogge, Peter D. Aplan, and R. Keith Humphries From the Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; the National Cancer Institute, Division of Clinical Sciences, Gaithersburg, MD; and the Department of Medicine, University of British Columbia, Vancouver, BC, Canada. HOX genes, notably members of the HOXA cluster, and HOX cofactors have increasingly been linked to human leukemia. Intriguingly, HOXD13, a member of the HOXD cluster not normally expressed in hematopoietic cells, was recently identified as a partner of NUP98 in a t(2;11) translocation associated with t-AML/MDS. We have now tested directly the leukemogenic potential of the NUP98-HOXD13 t(2; 11) fusion gene in the murine hematopoietic model. NUP98-HOXD13 strongly promoted growth and impaired differentiation of early hematopoietic progenitor cells in vitro; this effect was dependent on the NUP98 portion and an intact HOXD13 homeodomain. Expression of the NUP98-HOXD13 fusion gene in vivo resulted in a partial impairment of lymphopoiesis but did not induce evident hematologic disease until late after transplantation (more than 5 months), when some mice developed a myeloproliferative-like disease. In contrast, mice transplanted with bone marrow (BM) cells cotransduced with NUP98-HOXD13 and the HOX cofactor Meis1 rapidly developed lethal and transplantable acute myeloid leukemia (AML), with a median disease onset of 75 days. In summary, this study demonstrates that NUP98-HOXD13 can be directly implicated in the molecular process leading to leukemic transformation, and it supports a model in which the transforming properties of NUP98-HOXD13 are mediated through HOX-dependent pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. W. Choi, Y. J. Chung, C. Slape, and P. D. Aplan A NUP98-HOXD13 Fusion Gene Impairs Differentiation of B and T Lymphocytes and Leads to Expansion of Thymocytes with Partial TCRB Gene Rearrangement J. Immunol., November 15, 2009; 183(10): 6227 - 6235. [Abstract] [Full Text] [PDF] M. Heuser, L. M. Sly, B. Argiropoulos, F. Kuchenbauer, C. Lai, A. Weng, M. Leung, G. Lin, C. Brookes, S. Fung, et al. Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal Blood, November 5, 2009; 114(19): 3983 - 3993. [Abstract] [Full Text] [PDF] M. Heuser, D. B. Yap, M. Leung, T. R. de Algara, A. Tafech, S. McKinney, J. Dixon, R. Thresher, B. Colledge, M. Carlton, et al. Loss of Mll5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation Blood, February 12, 2009; 113(7): 1432 - 1443. [Abstract] [Full Text] [PDF] F. Kuchenbauer, R. D. Morin, B. Argiropoulos, O. I. Petriv, M. Griffith, M. Heuser, E. Yung, J. Piper, A. Delaney, A.-L. Prabhu, et al. In-depth characterization of the microRNA transcriptome in a leukemia progression model Genome Res., November 1, 2008; 18(11): 1787 - 1797. [Abstract] [Full Text] [PDF] Y. J. Chung, C. W. Choi, C. Slape, T. Fry, and P. D. Aplan Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell PNAS, September 16, 2008; 105(37): 14088 - 14093. [Abstract] [Full Text] [PDF] C. Slape, Y. W. Lin, H. Hartung, Z. Zhang, L. Wolff, and P. D. Aplan NUP98-HOX Translocations Lead to Myelodysplastic Syndrome in Mice and Men J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 64 - 68. [Abstract] [Full Text] [PDF] D. Jankovic, P. Gorello, T. Liu, S. Ehret, R. La Starza, C. Desjobert, F. Baty, M. Brutsche, P.-S. Jayaraman, A. Santoro, et al. Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia Blood, June 15, 2008; 111(12): 5672 - 5682. [Abstract] [Full Text] [PDF] S. D. Nimer Myelodysplastic syndromes Blood, May 15, 2008; 111(10): 4841 - 4851. [Abstract] [Full Text] [PDF] C. Hoemme, A. Peerzada, G. Behre, Y. Wang, M. McClelland, K. Nieselt, M. Zschunke, C. Disselhoff, S. Agrawal, F. Isken, et al. Chromatin modifications induced by PML-RAR{alpha} repress critical targets in leukemogenesis as analyzed by ChIP-Chip Blood, March 1, 2008; 111(5): 2887 - 2895. [Abstract] [Full Text] [PDF] V. P. S. Rawat, S. Thoene, V. M. Naidu, N. Arseni, B. Heilmeier, K. Metzeler, K. Petropoulos, A. Deshpande, L. Quintanilla-Martinez, S. K. Bohlander, et al. Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia Blood, January 1, 2008; 111(1): 309 - 319. [Abstract] [Full Text] [PDF] B. Argiropoulos, E. Yung, and R. K. Humphries Unraveling the crucial roles of Meis1 in leukemogenesis and normal hematopoiesis Genes & Dev., November 15, 2007; 21(22): 2845 - 2849. [Full Text] [PDF] D. Caudell, Z. Zhang, Y. J. Chung, and P. D. Aplan Expression of a CALM-AF10 Fusion Gene Leads to Hoxa Cluster Overexpression and Acute Leukemia in Transgenic Mice Cancer Res., September 1, 2007; 67(17): 8022 - 8031. [Abstract] [Full Text] [PDF] M. Heuser, B. Argiropoulos, F. Kuchenbauer, E. Yung, J. Piper, S. Fung, R. F. Schlenk, K. Dohner, T. Hinrichsen, C. Rudolph, et al. MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML Blood, September 1, 2007; 110(5): 1639 - 1647. [Abstract] [Full Text] [PDF] C. Slape, H. Hartung, Y.-W. Lin, J. Bies, L. Wolff, and P. D. Aplan Retroviral Insertional Mutagenesis Identifies Genes that Collaborate with NUP98-HOXD13 during Leukemic Transformation Cancer Res., June 1, 2007; 67(11): 5148 - 5155. [Abstract] [Full Text] [PDF] D. Bansal, C. Scholl, S. Frohling, E. McDowell, B. H. Lee, K. Dohner, P. Ernst, A. J. Davidson, G. Q. Daley, L. I. Zon, et al. Cdx4 dysregulates Hox gene expression and generates acute myeloid leukemia alone and in cooperation with Meis1a in a murine model PNAS, November 7, 2006; 103(45): 16924 - 16929. [Abstract] [Full Text] [PDF] L. Palmqvist, B. Argiropoulos, N. Pineault, C. Abramovich, L. M. Sly, G. Krystal, A. Wan, and R. K. Humphries The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia Blood, August 1, 2006; 108(3): 1030 - 1036. [Abstract] [Full Text] [PDF] A. Mamo, J. Krosl, E. Kroon, J. Bijl, A. Thompson, N. Mayotte, S. Girard, R. Bisaillon, N. Beslu, M. Featherstone, et al. Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation Blood, July 15, 2006; 108(2): 622 - 629. [Abstract] [Full Text] [PDF] X.-T. Bai, B.-W. Gu, T. Yin, C. Niu, X.-D. Xi, J. Zhang, Z. Chen, and S.-J. Chen Trans-Repressive Effect of NUP98-PMX1 on PMX1-Regulated c-FOS Gene through Recruitment of Histone Deacetylase 1 by FG Repeats. Cancer Res., May 1, 2006; 66(9): 4584 - 4590. [Abstract] [Full Text] [PDF] Y.-W. Lin, C. Slape, Z. Zhang, and P. D. Aplan NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia Blood, July 1, 2005; 106(1): 287 - 295. [Abstract] [Full Text] [PDF] P. J. Wermuth and A. M. Buchberg Meis1-mediated apoptosis is caspase dependent and can be suppressed by coexpression of HoxA9 in murine and human cell lines Blood, February 1, 2005; 105(3): 1222 - 1230. [Abstract] [Full Text] [PDF] N. Beslu, J. Krosl, M. Laurin, N. Mayotte, K. R. Humphries, and G. Sauvageau Molecular interactions involved in HOXB4-induced activation of HSC self-renewal Blood, October 15, 2004; 104(8): 2307 - 2314. [Abstract] [Full Text] [PDF] R. M. Gurevich, P. D. Aplan, and R. K. Humphries NUP98-Topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation Blood, August 15, 2004; 104(4): 1127 - 1136. [Abstract] [Full Text] [PDF] N. Pineault, C. Abramovich, H. Ohta, and R. K. Humphries Differential and Common Leukemogenic Potentials of Multiple NUP98-Hox Fusion Proteins Alone or with Meis1 Mol. Cell. Biol., March 1, 2004; 24(5): 1907 - 1917. [Abstract] [Full Text] [PDF] V. P. S. Rawat, M. Cusan, A. Deshpande, W. Hiddemann, L. Quintanilla-Martinez, R. K. Humphries, S. K. Bohlander, M. Feuring-Buske, and C. Buske Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukemia PNAS, January 20, 2004; 101(3): 817 - 822. [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]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020