Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.

ABSTRACT: Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis¹. These lesions are precursors for blood cancers^2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gen

SUBMITTER: Weinstock JS 

PROVIDER: S-EPMC10360040 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature