POT1 mutations identify inferior outcomes in chronic lymphocytic leukemia and disrupted telomere biology function

Telomere protection 1 (POT1) is an important subunit in the shelterin complex, considered the telomere protector. POT1 dysfunction may lead to telomere length dysregulation and genomic instability. Both germline and somatic POT1 mutations have been identified in CLL patients, suggesting the development of the disease. This study aimedto evaluate the occurrence of POT1 mutations throughout CLL's progression and determine their prognostic significance. Overall design: Our study included four hundred and forty-six patients with CLL from our center, including 390 TN (treatment-naive) patients and 56 R/R (relapse/refractory) patients. All patients were diagnosed from January 2017 to December 2022 based on International Workshop on CLL guidelines. Essential clinical characteristics and biological parameters were obtained from medical records. The next-generation sequencing panel included 126 common driver genes in lymphoid malignancies. To gain insight into the potential pathogenic mechanism of POT1 mutations in CLL, we performed RNA sequencing (RNA-seq) in three POT1 mutant and matched three wild-type CLL patients. All the differentially expressed genes (DEGs) were used to perform functional enrichment analysis to identify potential biological functions.