Measurable Residual Disease (MRD) Monitoring in Myeloproliferative Neoplasms

BCR::ABL1 negative myeloproliferative neoplasms (MPN) are driven predominantly by somatic mutations in JAK2, CALR, and MPL, which underpin diagnosis, prognostication, and measurable residual disease (MRD) monitoring. Advances in molecular assays have improved sensitivity for detecting canonical drivers and additional mutations across the MPN spectrum. In this review we evaluate current and emerging molecular methodologies for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We review the utility of PCR-based approaches, including allele-specific PCR, real-time quantitative PCR, and droplet digital PCR (ddPCR). Advances in ddPCR demonstrate precision and lower limits of detection for JAK2 V617F, CALR, and non-driver mutations, thus supporting the expanding role of ddPCR in MRD monitoring and relapse prediction. Recent advances in NGS techniques provide targeted profiling, enabling identification of possible co-occurring driver mutations and additional mutations associated with disease progression, treatment resistance, and leukemic transformation. Collectively, emerging workflows complement established gold-standard methodologies, while offering enhanced analytical performance and deeper pathological insight across the MPN spectrum. Optimal method selection requires balancing assay sensitivity, cost, and clinical utility. Advances in ddPCR and NGS methodologies have applicability for MRD monitoring in MPN and are powerful tools for detection of heterogenous and co-occurrent mutations across the MPN spectrum.