SEARCH:   Advanced

Blood, 1 April 2008, Vol. 111, No. 7, pp. 3735-3741. Prepublished online as a Blood First Edition Paper on January 17, 2008; DOI 10.1182/blood-2007-07-102533. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-07-102533v1 111/7/3735    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Roche-Lestienne, C. Articles by Preudhomme, C. Search for Related Content PubMed PubMed Citation Articles by Roche-Lestienne, C. Articles by Preudhomme, C. Related Collections Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 Catherine Roche-Lestienne1,2, Lauréline Deluche1, Sélim Corm3, Isabelle Tigaud4, Sami Joha1, Nathalie Philippe5, Sandrine Geffroy5, Jean-Luc Laï2, Franck-Emmanuel Nicolini6, Claude Preudhomme, on behalf of the Fi-LMC group1,5 1 Cancer Research Institute of Lille, JP Aubert Center, Inserm Unit 837, Lille, and North-West Cancéropôle; 2 Laboratory for Medical Genetics Centre Hospitalier Régional Universitaire (CHRU), Lille; 3 Hematology Department, CHRU, Lille; 4 Laboratory for Hematology and Cytogenetics, Centre Hospitalier Lyon Sud (CHLS), Pierre-Bénite; 5 Laboratory for Hematology, Biology and Pathology Center, CHRU, Lille; and 6 Hematology Department, E. Herriot Hospital, Lyon, France Acquired molecular abnormalities (mutations or chromosomal translocations) of the RUNX1 transcription factor gene are frequent in acute myeloblastic leukemias (AMLs) and in therapy-related myelodysplastic syndromes, but rarely in acute lymphoblastic leukemias (ALLs) and chronic myelogenous leukemias (CMLs). Among 18 BCR-ABL+ leukemias presenting acquired trisomy of chromosome 21, we report a high frequency (33%) of recurrent point mutations (4 in myeloid blast crisis [BC] CML and one in chronic phase CML) within the DNA-binding region of RUNX1. We did not found any mutation in de novo BCR-ABL+ ALLs or lymphoid BC CML. Emergence of the RUNX1 mutations was detected at diagnosis or before the acquisition of trisomy 21 during disease progression. In addition, we also report a high frequency of cryptic chromosomal RUNX1 translocation to a novel recently described gene partner, PRDM16 on chromosome 1p36, for 3 (21.4%) of 14 investigated patients: 2 myeloid BC CMLs and, for the first time, 1 therapy-related BCR-ABL+ ALL. Two patients presented both RUNX1 mutations and RUNX1-PRDM16 fusion. These events are associated with a short survival and support the concept of a cooperative effect of BCR-ABL with molecular RUNX1 abnormalities on the differentiation arrest phenotype observed during progression of CML and in BCR-ABL+ ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020