Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia
Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Department of Neurobiology
Life Sciences | Medicine and Health Sciences
The acute myeloid leukemia (AML)-associated CBF beta-SMMHC fusion protein impairs hematopoietic differentiation and predisposes to leukemic transformation. The mechanism of leukemia progression, however, is poorly understood. In this study, we report a conditional Cbfb-MYH11 knockin mouse model that develops AML with a median latency of 5 months. Cbf beta-SMMHC expression reduced the multilineage repopulation capacity of hematopoietic stem cells (HSCs) while maintaining their numbers under competitive conditions. The fusion protein induced abnormal myeloid progenitors (AMPs) with limited proliferative potential but leukemic predisposition similar to that of HSCs in transplanted mice. In addition, Cbf beta-SMMHC blocked megakaryocytic maturation at the CFU-Meg to megakaryocyte transition. These data show that a leukemia oncoprotein can inhibit differentiation and proliferation while not affecting the maintenance of long-term HSCs.
DOI of Published Version
Cancer Cell. 2006 Jan;9(1):57-68. Link to article on publisher's site
Kuo Y, Landrette SF, Heilman SA, Perrat PN, Garrett L, Liu PP, Le Beau MM, Kogan SC, Castilla LH. (2006). Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia. GSBS Student Publications. https://doi.org/10.1016/j.ccr.2005.12.014. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/628