Non-MPL-W515K/L mutations in myeloproliferative neoplasms: Insights from two case reports and a review of the literature.

BACKGROUND

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) result from clonal proliferation of hematopoietic stem cells, and include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Key driver mutations in the JAK2, CALR, and MPL genes are important for diagnosis and differentiation of triple-negative cases. The MPL gene, particularly exon 10, harbors mutation hotspots influencing pathogenesis and prognosis.

RESEARCH DESIGN AND

METHODS

This study presents two cases of atypical MPL mutations in MPN-patients and investigates the prevalence of non-canonical MPL mutations in the literature.

RESULTS

We report two MPN cases with non-canonical MPL mutations (S204P and W515R) detected by next-generation sequencing. We also conducted a systematic review of the PubMed database, identifying 67 cases of non-W515L/K MPL mutations. A total of 84 mutations were identified, comprised of 30 unique non-canonical mutations. W515R/S/A were the most frequent (32%), followed by V501A/M (15%) and S505N/C (13%). About 58% of patients had ET, 25% PMF and 13% post-ET/PV MF. Most mutations (69%) occurred in exon 10. About 26% harbored concurrent JAK2, CALR and MPL mutations.

CONCLUSIONS

Our findings highlight the importance of non-canonical mutations in diagnosis of MPN to prevent misclassification and improve patient management. Understanding these mutations may lead to more tailored treatments and better outcomes in MPN patients.