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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-04-1244. This Article Full Text (PDF) All Versions of this Article: 2002-04-1244v1 100/12/4177    most recent Alert me when this article is cited Alert me if a correction is posted 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 Mayotte, N. Articles by Sauvageau, G. Search for Related Content PubMed PubMed Citation Articles by Mayotte, N. Articles by Sauvageau, G. Social Bookmarking                   What's this? Submitted April 26, 2002 Accepted July 15, 2002 Oncogenic interaction between BCR-ABL and NUP98-HOXA9 demonstrated by the use of an in vitro purging culture system Nadine Mayotte, Denis-Claude Roy, Jing Yao, Evert Kroon, and Guy Sauvageau* Laboratory of Molecular Genetics of Stem Cells, Clinical Research Institute of Montreal, Montreal, PQ, Canada; Department of Medecine, University of Montreal, Montreal, QC, Canada; Division of Hematology, Maisoneuve-Rosemont Hospital, Montreal, QC, Canada Department of Medecine, University of Montreal, Montreal, PQ, Canada; Division of Hematology, Maisoneuve-Rosemont Hospital, Montreal, PQ, Canada Laboratory of Molecular Genetics of Stem Cells, Clinical Research Institute of Montreal, Montreal, PQ, Canada; Division of Hematology, Maisoneuve-Rosemont Hospital, Montreal, QC, Canada Laboratory of Molecular Genetics of Stem Cells, Clinical Research Institute of Montreal, Montreal, PQ, Canada Laboratory of Molecular Genetics of Stem Cells, Clinical Research Institute of Montreal, Montreal, PQ, Canada; Department of Medecine, University of Montreal, Montreal, PQ, Canada; Division of Hematology, Maisoneuve-Rosemont Hospital, Montreal, PQ, Canada * Corresponding author; email: sauvagg{at}ircm.qc.ca. Chronic myelogenous leukemia (CML) is a clonal stem cell disease caused by the BCR-ABL oncoprotein and is characterized, in its early phase, by excessive accumulation of mature myeloid cells which eventually leads to acute leukemia. The genetic events involved in CML progression to acute leukemia remain largely unknown. Recent studies have detected the presence of the NUP98-HOXA9 fusion oncogene in acute leukemia derived from CML patients which suggests that these 2 oncoproteins may interact and influence CML disease progression. Using in vitro purging of BCR-ABL-transduced mouse bone marrow cells, we can now report that recipients of bone marrow cells engineered to co-express BCR-ABL with NUP98-HOXA9 develop acute leukemia within 7-10 days post-transplantation. However no disease is detected for over 2 months in mice transplanted with bone marrow cells expressing either BCR-ABL or NUP98-HOXA9. We also provide evidence of high levels of HOXA9 expressed in leukemic blasts from acute phase CML patients and that it interacts significantly on a genetic level with BCR-ABL in our in vivo CML model. Together, these studies support a causative, as opposed to a consequential, role for NUP98-HOXA9 (and possibly HOXA9) in CML disease progression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Roche-Lestienne, L. Deluche, S. Corm, I. Tigaud, S. Joha, N. Philippe, S. Geffroy, J.-L. Lai, F.-E. Nicolini, C. Preudhomme, et al. RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance Blood, April 1, 2008; 111(7): 3735 - 3741. [Abstract] [Full Text] [PDF] S. J. Neering, T. Bushnell, S. Sozer, J. Ashton, R. M. Rossi, P.-Y. Wang, D. R. Bell, D. Heinrich, A. 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