Clonal Hematopoiesis: Updates and Implications at the Solid Tumor-Immune Interface

Abstract

Recent larger-scale studies of patients with cancer and longitudinal population cohorts have revealed how age-related expansions of mutant hematopoietic cells (clonal hematopoiesis [CH]) have differential associations with incident and prevalent cancers and their outcomes. Increasing recognition and deeper understanding of genetic subtypes of CH are yielding insights into the tumor-immune interface that may help to explain the heterogeneous impact of CH on tumorigenesis and treatment. Herein, we update the expanding influence of CH in precision oncology and propose important research and clinical questions to address to effectively manage and harness CH in oncology patients.

Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy

“…Our approach also for the first time provides evidence of the occurrence of clonal hematopoiesis ( 43 ). Further studies will enable us to determine the potential role or contribution of clonal hematopoiesis to tumor progression.…”

“…Alterations possibly linked to clonal hematopoiesis were observed in cfDNA samples during follow-up, in genes such as DNMT3B or SETDB1 in patient 18, or BCOR or JAK3 in patient 16, with a VAF remaining below 2% in the cfDNA ( 43 ). Although no whole blood cell (WBC) pellet was available to provide proof of the hematologic origin of these alterations in patient 18, an enrichment of the VAF of BCOR and JAK3 in the WBC pellet obtained after treatment was observed for patient 16, strongly suggesting clonal hematopoiesis.…”

Circulating cell-free (cf)DNA analysis: Current technologies and applications in gynecologic cancer

“…The main source of biological noise in cfDNA analyses is clonal hematopoiesis (CH) ( Hu et al, 2018 ). CH is a part of the normal process of aging and involves the accumulation of somatic mutations in hematopoietic stem cells and their clonal expansion in blood cells ( Buttigieg and Rauh, 2023 ). Importantly, and as mentioned above, most non-cancerous cfDNA in plasma originates from hematopoietic cells.…”