Stem cell regulation and dynamics in myeloid malignancies.

In this issue of PIH, we asked four researchers to write about basic research on the molecular mechanisms of the development of myeloid malignancies, in particular two epigenetic regulation and two space- and time-dependent factors. Regarding epigenomic regulation, Dr. Yang reviewed ASXL1, a polycomb modifier gene that is often mutated in myeloid malignancies, but also in clonal hematopoiesis in healthy elderly people, and Dr. Vu reviewed RNA modifications, which are critical for development and tissue homeostasis, and are now recognized as an important driver for cancer development. Regarding spatiotemporal factors, Dr. Inoue reviewed the role of extracellular vesicles in leukemic stem cell niches. As some cancers develop preferentially in infancy or old age, Dr. Osato discussed the time-specific development of leukemia involving the RUNX1-ETO mutation, which is often found in leukemia in adolescents and young adults. Recent studies on hematopoietic development have shown that hematopoietic stem cells do not generate multipotent progenitor cells, but that these cells develop in parallel. We hope that reconsideration of the definition of leukemic stem cells and their origin will help us understand the regulatory mechanisms of these cells, but also enable us to develop future therapies by targeting factors that regulate the leukemic stem cell and the niche.