Genetic compensation of RUNX family transcription factors in leukemia

Runt (Runt domain)-related transcription factor 1 (RUNX1) is a transcription factor belonging to the core-binding factor (CBF) family. It is considered to be a master regulator of hematopoiesis and has been regarded as a tumor suppressor because it is essential for definitive hematopoiesis in vertebrates. It is one of the most frequent target genes of chromosomal translocation in leukemia, and germ line mutation of RUNX1 causes familial platelet disorder with associated myeloid malignancies. Somatic cell mutations and chromosomal abnormalities, including those of RUNX1, are observed in myelodysplastic syndrome, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myelomonocytic leukemia at a high frequency. In addition, recent studies reported by us and other groups suggested that WT RUNX1 is needed for survival and proliferation of certain types of leukemia. In this review, we describe the significance and paradoxical requirement of RUNX1 tumor suppressor in hematological malignancies based on recent findings such as "Genetic compensation of RUNX family transcription factors in leukemia," "RUNX1 inhibition-induced inhibitory effects on leukemia cells through p53 activation" and our novel promising theory "Cluster regulation of RUNX (CROX)" through the RUNX gene switch method using pyrrole-imidazole polyamides as a new technique that could contribute to the next generation of leukemia treatment strategies.