JAK2 V617F as a diagnostic and prognostic biomarker in myeloproliferative neoplasms

Molecular analysis of BCR-ABL1-negative myeloproliferative neoplasms has shown a shared codon 617 substitution of JAK2 that leads to a constitutively active tyrosine kinase and a pathogenic lesion that unites all three polycythemia vera, essential thrombocythemia, and primary myelofibrosis. This mutation interferes with the autoinhibitory regulation and results in persistent downstream JAK-STAT signaling, and thereafter, myeloid, megakaryocytic, and inappropriate erythroid proliferation. JAK2 V617F has emerged as a major molecular biomarker in the diagnostic workup and classification of myeloproliferative neoplasms in laboratory medicine when used together with blood counts, bone marrow morphology, serum erythropoietin, and other molecular markers, such as CALR and MPL. Outside its diagnostic application, variant allele burden has also been linked to thrombosis, disease phenotype, clonal growth, fibrotic development, and survival but not uniformly across disease subtypes and clinical contexts. JAK2 V617F detection in laboratories has moved beyond traditional approaches based on PCR to sensitive quantitative technologies, such as digital PCR and next-generation sequencing-based technologies, making the standardization of assays, assurance of quality and more clinically integrated interpretation more important. In general, JAK2 V617F is an effective prognostic and diagnostic biomarker in myeloproliferative neoplasms. It can be further enhanced in diagnostic laboratory hematology with further optimization of the strategies of molecular testing, reporting systems, and multi-marker diagnostic algorithms.