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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5190-5192. Prepublished online as a Blood First Edition Paper on September 22, 2008; DOI 10.1182/blood-2008-04-148791. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-148791v1 112/13/5190    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 Jones, D. Articles by Jorgensen, J. L. Search for Related Content PubMed PubMed Citation Articles by Jones, D. Articles by Jorgensen, J. L. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report BCR-ABL fusion transcript types and levels and their interaction with secondary genetic changes in determining the phenotype of Philadelphia chromosome–positive leukemias Dan Jones1, Rajyalakshmi Luthra1, Jorge Cortes2, Deborah Thomas2, Susan O'Brien2, Carlos Bueso-Ramos1, Seema Hai1, Farhad Ravandi2, Marcos de Lima3, Hagop Kantarjian2, and Jeffrey L. Jorgensen1 Departments of 1 Hematopathology, 2 Leukemia, and 3 Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston It remains unresolved how different BCR-ABL transcripts differentially drive lymphoid and myeloid proliferation in Philadelphia chromosome–positive (Ph+) leukemias. We compared BCR-ABL transcript type and level with kinase domain (KD) mutation status, genotype, and phenotype in 1855 Ph+ leukemias. Compared with e1a2/p190 BCR-ABL cases, de novo e13-e14a2/p210 Ph+ lymphoid leukemia more frequently showed CML-type background, had higher blast-normalized BCR-ABL transcript levels, and more frequent persistent BCR-ABL transcript in the absence of detectable lymphoblasts. Secondary lymphoid blast transformation of CML was exclusively due to e13/e14a2/p210 BCR-ABL but was associated, at a much higher level than p210 myeloid transformation, with acquisition of new KD mutations and/or Ph genomic amplification. In contrast, myeloid blast transformation was more frequently accompanied by new acquisition of acute myeloid leukemia-type chromosomal aberrations, particularly involving the EVI1 and RUNX1 loci. Therefore, higher kinase activity by mutation, transcriptional up-regulation or gene amplification appears required for lymphoid transformation by p210 BCR-ABL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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