Lymphoid clonal hematopoiesis: implications for malignancy, immunity, and treatment

Clonal hematopoiesis (CH) is the age-related expansion of hematopoietic stem cell clones caused by the acquisition of somatic point mutations or mosaic chromosomal alterations (mCAs). Clonal hematopoiesis caused by somatic mutations has primarily been associated with increased risk of myeloid malignancies, while mCAs have been associated with increased risk of lymphoid malignancies. A recent study by Niroula et al. challenged this paradigm by finding a distinct subset of somatic mutations and mCAs that are associated with increased risk of lymphoid malignancy. CH driven by these mutations is termed lymphoid clonal hematopoiesis (L-CH). Unlike myeloid clonal hematopoiesis (M-CH), L-CH has the potential to originate at both stem cells and partially or fully differentiated progeny stages of maturation. In this review, we explore the definition of L-CH in the context of lymphocyte maturation and lymphoid malignancy precursor disorders, the evidence for L-CH in late-onset autoimmunity and immunodeficiency, and the development of therapy-related L-CH following chemotherapy or hematopoietic stem cell transplantation.

Automated summary

Clonal hematopoiesis (CH) is the expansion of hematopoietic stem cell clones due to acquired somatic mutations or mosaic chromosomal alterations. While somatic mutations are associated with myeloid malignancies, a recent study discovered a subset of mutations and chromosomal alterations that are specifically associated with lymphoid malignancies, termed lymphoid clonal hematopoiesis (L-CH). Unlike myeloid clonal hematopoiesis, L-CH can originate from both stem cells and differentiated progeny stages. This review explores the definition of L-CH in the context of lymphocyte maturation and lymphoid malignancy precursor disorders, its association with late-onset autoimmunity and immunodeficiency, as well as therapy-related L-CH following chemotherapy or hematopoietic stem cell transplantation.