Clonal hematopoiesis in idiopathic cytopenia of undetermined significance

Abstract

Abstract The mutation landscapes and clinical significance of clonal hematopoiesis (CH) in idiopathic cytopenia of undetermined significance (ICUS) is still unclear. Based on the next-generation sequencingdata of 281 ICUS patients, we sought to depict the profile of CH in ICUS and evaluate its role in disease progression. It was found that CH occurred in 27% of the patients, and was more prevalent in male patients. The incidence of CH accumulated with age. AXSL1, DNMT3A, U2AF1 and TET2 were the most frequently mutated genes. Exclusive mutations existed in DNMT3A and U2AF1, and co-occurring mutations were found between SRSF2 and TET2, SRSF2 and WT1. Fifteen of the 281 ICUS patients transformed to hematological malignancies, and CH group had a higher incidence of leukemic transformation than non-CH group. Variant allele frequencies (VAFs) of the mutated genes, such asASXL1, U2AF1 and TP53, showed an obvious elevation after disease transformation. Moreover, CH patients had a shorter overall survival and progression-free survival. These data indicated that CH was a common phenomenon in ICUS patients, and it contributed greatly to the increased risk of disease progression, suggesting the significance of gene mutation monitoring in ICUS management.