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Myeloid neoplasms and clonal hematopoiesis from the RUNX1 perspective

Leukemia volume 36, pages 1203–1214 (2022)Cite this article

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Abstract

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.

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Fig. 1: Protein structure of the major RUNX1 isoforms.
Fig. 2: RUNX1-related chromosomal alteration.
Fig. 3: Pathogenic mutations in the RUXN1 gene.
Fig. 4: Cell-intrinsic/-extrinsic effects of RUNX1 mutation.

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  1. Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    Yoshihiro Hayashi, Yuka Harada & Hironori Harada

  2. Department of Clinical Laboratory, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

    Yuka Harada

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  1. Yoshihiro Hayashi
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YH and YHar reviewed the literature and wrote the paper; HH edited the paper.

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Hayashi, Y., Harada, Y. & Harada, H. Myeloid neoplasms and clonal hematopoiesis from the RUNX1 perspective. Leukemia 36, 1203–1214 (2022). https://doi.org/10.1038/s41375-022-01548-7

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