Supplementary Material for: Clonal Megakaryocyte Dysplasia with Isolated Thrombocytosis Is a Distinct Myeloproliferative Neoplasm Phenotype

<b><i>Introduction:</i></b> About 15% of people with a myeloproliferative neoplasm (MPN) are identified as <i>MPN, unclassifiable</i> using the 2016 WHO classification. <b><i>Methods:</i></b> We tested whether persons with platelet concentration ≥450 × 10E+9/L, bone marrow megakaryocyte morphology typical of prefibrotic/early myelofibrosis (pre-MF), and no minor criteria of pre-MF should be classified as a distinct MPN subtype, <i>clonal megakaryocyte dysplasia with isolated thrombocytosis</i> (CMD-IT). <b><i>Results:</i></b> 139 subjects meet these criteria who we compared with primary myelofibrosis (PMF) including 402 with pre-MF and 521 with overt myelofibrosis. CMD-IT subjects were more likely female and younger. They had lower frequencies of <i>JAK2</i>^V617F compared with persons with PMF (55% vs. 70%; <i>p</i> &lt; 0.001) and higher frequencies of <i>CALR</i> mutations (37% vs. 17%; <i>p</i> &lt; 0.001). They also had lower frequency of variations associated with <i>JAK2</i>^V617F susceptibility, <i>JAK2</i> 46/1 (35% vs. 47%; <i>p</i> = 0.021), and <i>VEGFA</i> rs3025039 (12% vs. 17%; <i>p</i> = 0.030). Subjects with CMD-IT had lower incidences of thrombotic events compared with those with pre-MF (9.7% vs. 26%; <i>p</i> &lt; 0.001) and longer survival (median, not reached vs. 23 years; HR = 0.34 (0.10, 0.30); <i>p</i> &lt; 0.001). <b><i>Conclusion:</i></b> Our data indicate CMD-IT is a distinct MPN subtype and should be included in the classification of myeloid neoplasms.