| Literature DB >> 16413472 |
Ya-Huei Kuo1, Sean F Landrette, Susan A Heilman, Paola N Perrat, Lisa Garrett, Pu P Liu, Michelle M Le Beau, Scott C Kogan, Lucio H Castilla.
Abstract
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.Entities:
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Year: 2006 PMID： 16413472 DOI： 10.1016/j.ccr.2005.12.014
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 38.585