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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4771-4779. Prepublished online as a Blood First Edition Paper on January 28, 2008; DOI 10.1182/blood-2007-08-105072. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-08-105072v1 111/9/4771    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 Google Scholar Articles by Lidonnici, M. R. Articles by Calabretta, B. PubMed PubMed Citation Articles by Lidonnici, M. R. Articles by Calabretta, B. Related Collections Oncogenes and Tumor Suppressors Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Requirement of c-Myb for p210BCR/ABL-dependent transformation of hematopoietic progenitors and leukemogenesis Maria Rosa Lidonnici1, Francesca Corradini2, Todd Waldron1, Timothy P. Bender3, and Bruno Calabretta1 1 Department of Cancer Biology, and Kimmel Cancer Center, Thomas Jefferson University Medical College, Philadelphia, PA; 2 Department of Biomedical Sciences, University of Modena Medical School, Modena, Italy; and 3 Department of Microbiology, University of Virginia Health System, Charlottesville The c-Myb gene encodes a transcription factor required for proliferation and survival of normal myeloid progenitors and leukemic blast cells. Targeting of c-Myb by antisense oligodeoxynucleotides has suggested that myeloid leukemia blasts (including chronic myelogenous leukemia [CML]–blast crisis cells) rely on c-Myb expression more than normal progenitors, but a genetic approach to assess the requirement of c-Myb by p210BCR/ABL-transformed hematopoietic progenitors has not been taken. We show here that loss of a c-Myb allele had modest effects (20%-28% decrease) on colony formation of nontransduced progenitors, while the effect on p210BCR/ABL-expressing Lin– Sca-1+ and Lin– Sca-1+Kit+ cells was more pronounced (50%-80% decrease). Using a model of CML-blast crisis, mice (n = 14) injected with p210BCR/ABL-transduced p53–/–c-Mybw/w marrow cells developed leukemia rapidly and had a median survival of 26 days, while only 67% of mice (n = 12) injected with p210BCR/ABL-transduced p53–/–c-Mybw/d marrow cells died of leukemia with a median survival of 96 days. p210BCR/ABL-transduced c-Mybw/w and c-Mybw/d marrow progenitors expressed similar levels of the c-Myb–regulated genes c-Myc and cyclin B1, while those of Bcl-2 were reduced. However, ectopic Bcl-2 expression did not enhance colony formation of p210BCR/ABL-transduced c-Mybw/d Lin–Sca-1+Kit+ cells. Together, these studies support the requirement of c-Myb for p210BCR/ABL-dependent leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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