Abstract 5061: Induction of B cell acute lymphoblastic leukemia by BCR/ABL requires c-Myb and its activation of Bmi-1

Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL), carrying the e1a2 fusion BCR/ABL oncogene, is typically an aggressive B cell leukemia, often resistant to current treatment options. The transcription factor c-Myb plays a critical role in B cell development, but its role in B cell leukemia is unknown. To study the role of c-Myb in BCR/ABL-induced lymphoblastic leukemia, we compared disease induction, latency and survival in mice expressing the BCR/ABL transgene in a c-Myb knockout versus a wild-type background. BCR/ABL+Myb+/− mice show a distinct leukemia-resistant phenotype, whereas, BCR/ABL+Myb+/+ mice exhibit rapid induction of disease with shortened survival. Using microarray analysis to examine differential gene expression, we have identified putative downstream targets of c-Myb which play a role in leukemogenesis. Subsequent use of gene overexpression, RNAi for target gene knockdown and chIP have identified the polycomb gene, Bmi-1, as a target of c-Myb transactivation. Furthermore, inhibition of the p19ARF tumor suppressor, a Bmi-1 target, may be essential to the induction of ALL by BCR/ABL. In this report, we describe the essential role that c-Myb and its activation of Bmi-1, play in BCR/ABL-induced leukemogenesis.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5061.

Duke Scholars

Author Terry Hyslop Biostatistics & Bioinformatics, Division of Translational Bi ...