The C-terminus of CBF-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis.

The C-terminus of CBF-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-mulimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBF-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBF-SMMHC (CBF-SMMHCC95). Embryos with a single copy of CBF-SMMHCDC95 were viable and showed no defects in hematopoiesis, while embryos homozygous for the CBF-SMMHCC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBF-SMMHCC95.

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Kamikubo Y, Hyde RK, Zhao L, Alemu L, Rivas C, Garrett LJ, Liu PP