Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System.

Abstract

Testing for somatic mutations in JAK2, MPL, and CALR genes is a crucial element in the diagnosis of myeloproliferative neoplasms (MPNs). This may have inadvertently led to increased requests for testing to rule out MPN, including clinical situations with low pretest probability. This article examines JAK2, MPL, and CALR testing by next-generation sequencing (NGS) with the goal of formulating practical guidelines to make test use more efficient and effective. NGS results from 1482 patients tested between 2015 and March 2022 were retrieved, along with corresponding bone marrow biopsies and complete blood cell count results performed within 90 days before NGS, and 245 cases (16.5%) were positive for pathogenic variants in JAK2, MPL, or CALR genes. The findings showed an increase in the proportion of positive cases with patient age, and a statistically significant difference in red blood cell counts and platelet counts among patients with positive versus negative results. Using these factors, simple algorithms were constructed to predict positive results with a maximum sensitivity of 91%, while potentially eliminating 28% of negative test results. However, these models still failed to identify approximately 9% of patients with MPNs. Among these missed patients, many had either primary myelofibrosis or myelodysplastic syndrome/MPN. Considering a simple triage model to help guide MPN testing could represent a more cost-effective approach, particularly if missed patients could be further reduced.