High frequency of germline ATM variants in familial philadelphia-negativew myeloproliferative neoplasm

Familial Philadelphia-negative myeloproliferative neoplasms (MPNs) represent a recognized subset of these clonal hematopoietic disorders, accounting for approximately 7%–8% of all MPN cases [1]. Population-based studies have demonstrated a high risk of MPNs among first-degree relatives of affected individuals, particularly in families with multiple affected members or in relatives of younger patients [2, 3]. Notably, familial and sporadic cases show no significant differences in clinical phenotype, disease complications, or risk of progression, suggesting that familial MPNs share the same disease biology and prognosis as their sporadic counterparts [4]. However, as in other familial cancers, second-generation individuals experience earlier disease onset or more aggressive phenotypes [5]. In addition, the spectrum of somatic mutations closely mirrors that of sporadic MPNs, with JAK2 V617F being the most common acquired driver mutation. Nevertheless, discordant somatic mutations are frequently observed among related individuals, suggesting that while shared germline factors may confer susceptibility to clonal hematopoiesis, the acquisition of specific driver mutations occurs stochastically and independently [6].