ArticleAnnals of hematology2026
NGS and emerging molecular scenarios in chronic myeloproliferative neoplasms: a case of double mutated polycythemia vera.
Article in Annals of hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders driven by mutually exclusive JAK2, CALR, MPL mutations. NGS has revealed rare cases with coexisting driver mutations, challenging classical diagnostic paradigms, highlighting clonal complexity. We describe a 71-year-old man with JAK2-positive polycythemia vera (PV) whose hematologic parameters remained suboptimally controlled under hydroxycarbamide treatment. Concern for disease progression prompted NGS analysis, surprisingly revealing a dominant CALR type 2 mutation alongside non-driver DNMT3A variants, while the JAK2 V617F clone was below the NGS limit of detection. Retrospective analysis confirmed dynamic clonal competition between the dominant CALR clone and the minor low VAF JAK2 clone, whereas histopathology remained consistent with PV, supporting an integrated diagnosis of MPN-NOS. This case demonstrates that additional mutated clones can significantly influence phenotype and disease evolution, highlighting the limitations of stepwise molecular testing. Comprehensive profiling of clonal architecture is essential to refine diagnosis and prognosis, in the NGS era.
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