GSBS Student Publications


Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Department of Neurobiology



Document Type


Medical Subject Headings

Acute Disease; Animals; B-Lymphocytes; Blood Platelets; Cell Proliferation; Hematopoiesis; Leukemia, Myeloid; Megakaryocytes; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Myeloid Progenitor Cells; Oncogene Proteins, Fusion; Preleukemia


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.

Rights and Permissions

Citation: Cancer Cell. 2006 Jan;9(1):57-68. Link to article on publisher's site

DOI of Published Version


Related Resources

Link to article in PubMed

Journal Title

Cancer cell

PubMed ID