Low V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional or Gene Mutations.

(Janus kinase 2) V617F, (Calreticulin) exon 9, and (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefore, after the emergence of one type of mutation, other types should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Our study includes DNA samples from 1958 patients with clinical evidence of MPN, admitted to the National Research Center for Hematology for genetic analysis between 2016 and 2019. In 315 of 1402 cases (22.6%), mutations were detected. In 23 of these 315 cases (7.3%), the JAK2 V617F mutation was found in addition to the mutation. In 16 from 24 (69.6%) cases, with combined and mutations, V617F allele burden was lower than 1%. A combination of V617F with W515L/K was also observed in 1 out of 1348 cases, only. allele burden in this case was also lower than 1%. Additional mutations may coexist over the low background of JAK2 V617F allele. Therefore, in cases of detecting MPNs with a low allelic load V617F, it may be advisable to search for other molecular markers, primarily mutations in exon 9 of . The load of the combined mutations measured at different time points may indicate that, at least in some cases, these mutations could be represented by different clones of malignant cells.