Issues

In this issue, clonal hematopoiesis (CH) as a predecessor of blood cancers is studied from public-health to submolecular scales, and from retrospecitve clonal evolution to future clinical trials. Kohnke et al. (p. 202) show that truncating ASXL1 mutations, recurrent in CH and AML, drive clonal expansion of human stem and hematopoietic progenitor cells (HSPC) by opposing PRC-mediated histone ubiquitination. Young et al. (p. 153) map territories of premalignant clones inside the human bone marrow. Saygin et al. (p. 164) identify a subgroup of adult acute lymphoblastic leukemia (ALL) with worse prognosis and resistance to chemotherapy originating from “myeloid” CH: multilineage progenitors with “myeloid” mutations predating ALL diagnosis for years. Ghobrial et al. (p. 146) offer regulatory considerations for future clinical trials intercepting high-risk CH.