Work

Clonal hematopoiesis driver mutations: molecular mechanisms and clinical implications - inclusive fitness of pre-leukemic hematopoietic stem and progenitor cells through pro-inflammatory features of their progeny

Year: 2026

Type: article

Abstract: Clonal hematopoiesis is driven by the age-associated expansion of hematopoietic stem and progenitor cells that harbor somatic driver mutations; however, the mechanisms underlying the long-term persistence of these cells remain incompletely understood. This review frames clonal hematopoiesis through the lens of inclusive fitness, proposing that mutant pre-leukemic hematopoietic stem and progenitor cells enhance their evolutionary success not only through intrinsic self-renewal advantages, but also via indirect effects mediated by their differentiated progeny. We synthesize evidence showing that mutant immune cells promote inflammatory microenvironments that selectively impair wild-type hematopoietic stem cells while reinforcing mutant self-renewal, establishing self-sustaining feedback loops that shape clonal dynamics and systemic disease risk.

Source: Haematologica

DOI: 10.3324/haematol.2025.287480

Authors: Tal Bachrach, Adrian Duek, Liran I. Shlush

Institutions: Weizmann Institute of Science, Ben-Gurion University of the Negev

Language: English

Topic: Acute Myeloid Leukemia Research

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,157