Premium
Role of c‐Myb in the survival of pre B‐cell acute lymphoblastic leukemia and leukemogenesis
Author(s) -
Sarvaiya Purvaba J.,
Schwartz Jason R.,
Hernandez Claudia P.,
Rodriguez Paulo C.,
Vedeckis Wayne V.
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23283
Subject(s) - lymphoblastic leukemia , cancer research , leukemia , medicine , myb , oncology , acute lymphocytic leukemia , immunology , biology , genetics , gene , transcription factor
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. The current treatment protocol for ALL involves an intense chemotherapy regimen yielding cure rates of nearly 80%. However, new therapies need to be designed not only to increase the survival rate but also to combat the risk of severe therapy associated toxicities including secondary malignancies, growth problems, organ damage, and infertility. The c‐Myb proto‐oncogene is highly expressed in immature hematopoietic cells. In this study, we demonstrate that loss of c‐Myb itself decreased the viability of these leukemic cells. Additionally, the inhibition of c‐Myb caused a decrease in cell proliferation, significantly increased the number of cells in G 0 /G 1 phase of the cell cycle, increased the sensitivity of pre‐B‐ALL cells to cytotoxic agents in vitro, and significantly delayed disease onset in a mouse model of leukemia. Furthermore, we demonstrate that Bcl‐2 is a target of c‐Myb in pre‐B‐ALL cells. Our results identify c‐Myb as a potential therapeutic target in pre‐B‐ALL and suggest that suppression of c‐Myb levels or activity, in combination with currently used therapies and/or dose reduction, may lead to a decrease in toxicity and an increase in patient survival rates. Because c‐Myb is aberrantly expressed in several other malignancies, targeting c‐Myb will have broad clinical applications. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.