Roles for RUNX1/AML1 in DNA damage-repair pathway

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We found that the C-terminal deletion mutant of RUNX1 attenuates DNA-damage repair responses in hematopoietic stem/progenitor cells. Bone marrow cells from MDS/AML patients harboring the RUNX1-C-terminal mutation showed significantly lower levels of GADD45A expression compared with those from MDS/AML patients with wild-type RUNX1. As for this mechanism, we found that RUNX1 directly regulates the transcription of GADD45A. These results suggest Gadd45a dysfunction due to RUNX1 mutations can cause additional mutation(s) required for multi-step leukemogenesis.