Inv(16)(p13q22) is associated with acute myeloid leukemia subtype M4Eo, which is characterized by the presence of myelomonocytic blasts and atypical eosinophils. This chromosomal rearrangement results in the fusion of CBFB and MYH11 genes. Mouse models indicate that the fusion gene, Cbfb-MYH11, inhibits differentiation of hematopoietic cells. Although expression of Cbfb-MYH11 is not sufficient for leukemogenesis, a combination of Cbfb-MYH11 and additional mutations can lead specifically to the development of myeloid leukemia. Normally, CBFβ interacts with CBFα to form a transcriptionally active nuclear complex. In vitro studies indicate that expression of CBFB-MYH11 leads to sequestration of CBFα2 in the cytoplasm. It also has been shown to inhibit CBF-mediated transactivation, slow cell cycle progression, delay the apoptotic response to DNA damaging agents, and protect CBFα2 from degradation. The importance of these functions in vivo remains to be determined.
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Correspondence to Pu Paul Liu, MD, PhD, Room 2A18, Building 49, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA; e-mail: firstname.lastname@example.org