[Dysregulated control of hematopoietic stem cells in myeloid malignancies]

Myeloid neoplasia comprises a spectrum of disorders now recognized as a continuum, ranging from clonal hematopoiesis to overt disease. Recent genomic studies have shown that hematopoietic stem cells (HSCs) harboring somatic mutations undergo clonal expansion long before clinical manifestation. Although these mutant stem cells often retain multilineage differentiation potential, their intrinsic functions-including self-renewal capacity and differentiation dynamics-are altered. In addition, accumulating evidence indicates that differentiated progeny derived from mutant stem cells exhibit functional abnormalities, such as dysregulated inflammatory responses and altered interactions with the bone marrow microenvironment. These alterations, spanning both stem cell and differentiated cell compartments, contribute to inflammatory conditions, remodeling of the bone marrow niche, and the establishment of a selective environment that promotes clonal expansion while impairing normal hematopoiesis. In this educational review, I summarize recent advances in understanding dysregulated HSC control in the early stages of myeloid neoplasia, with particular emphasis on aging, inflammation, immune interactions, and crosstalk with the bone marrow niche. Focusing on these early events underscores the importance of viewing myeloid neoplasia from its cellular and microenvironmental origins.