Accelerated leukemogenesis by truncated CBFb-SMMHC defective in high-affinity binding with RUNX1

Dominant RUNX1 inhibition has been proposed as a common pathway for CBF-leukemia. CBFb-SMMHC, a fusion protein in human acute myeloid leukemia (AML), dominantly inhibits RUNX1 largely through its RUNX1 high-affinity binding domain (HABD). We generated knock-in mice expressing CBFb-SMMHC with a HABD deletion, CBFb-SMMHCd179-221. These mice developed leukemia highly efficiently, even though hematopoietic defects associated with Runx1-inhibition were partially rescued.

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Kamikubo Y, Zhao L, Wunderlich M, Corpora T, Hyde RK, Paul TA, Kundu M, Garrett L, Compton S, Huang G, Wolff L, Ito Y, Bushweller J, Mulloy JC, Liu PP