Clonal megakaryocyte dysplasia with normal blood values: a covert, thrombosis-prone, early myeloproliferative...

To improve our knowledge on the epidemiological, clinical and pathobiological profile of clonal megakaryocyte dysplasia with normal blood values (CMD-NBV), a BCR::ABL-negative myeloproliferative neoplasms clinical variant, we here report a series of 30 consecutive subjects with CMD-NBV. Sixteen subjects were men and the median age was 48 years (interquartile range [IQR], 39-53 years). A situation-driven diagnosis (70% of cases had the diagnosis triggered by an incidental or symptomatic venous or arterial thrombosis), high incidence of thrombotic events (6.5 events x 100 subject-years), and indolent disease (the 10-year CMD-NBV-specific survival was 100%) were common. Nineteen subjects had a high body mass index at diagnosis and 14 had ≥1 Charlson co-morbidities. In 21 the driver variant was JAK2V617F with a median variant allele frequency at diagnosis of 8.9% (IQR, 5.4-18.4%). Six of 24 (25%) subjects with data on next-generation sequencing for myeloid neoplasm-related genes had ≥1 pathogenic somatic variant in ASXL1, TET2, DNMT3A or SRSF2, a frequency in the lower range of values of chronic myeloproliferative neoplasms. Twelve putative germline, non-pathogenic, missense variants in ASXL1, TET2, DNMT3A, RUNX1, CUX1, ABL1, NF1, KIT and CSF3R or 5' UTR in NF1 and 3' UTR in ASXL1 were detected in ten of 24 (42%) subjects. These data further support identification of CMD-NBV as a distinct entity.