RUNX1 is a critical transcription factor for the emergence of definitive hematopoiesis and the precise regulation of adult hematopoiesis. Dysregulation of its regulatory network causes aberrant hematopoiesis. Recurrent genetic alterations in RUNX1, including chromosomal translocations and mutations, have been identified in both inherited and sporadic diseases. Recent genomic studies have revealed a vast mutational landscape surrounding genetic alterations in RUNX1. Accumulating pieces of evidence also indicate the leukemogenic role of wild-type RUNX1 in certain situations. Based on these efforts, part of the molecular mechanisms of disease development as a consequence of dysregulated RUNX1-regulatory networks have become increasingly evident. This review highlights the recent advances in the field of RUNX1 research and discusses the critical roles of RUNX1 in hematopoiesis and the pathobiological function of its alterations in the context of disease, particularly myeloid neoplasms, and clonal hematopoiesis.
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.