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

Introduction: About 15% of people with a myeloproliferative neoplasm (MPN) are identified as MPN, unclassifiable using the 2016 WHO classification. Methods: 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, clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). Results: 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 JAK2V617F compared with persons with PMF (55% vs. 70%; p CALR mutations (37% vs. 17%; p JAK2V617F susceptibility, JAK2 46/1 (35% vs. 47%; p = 0.021), and VEGFA rs3025039 (12% vs. 17%; p = 0.030). Subjects with CMD-IT had lower incidences of thrombotic events compared with those with pre-MF (9.7% vs. 26%; p p Conclusion: Our data indicate CMD-IT is a distinct MPN subtype and should be included in the classification of myeloid neoplasms.引言：约15%的骨髓增殖性肿瘤（myeloproliferative neoplasm, MPN）患者无法通过2016年世界卫生组织（WHO）分类系统进行分型，被归为未分类MPN。 方法：本研究旨在验证，对于血小板计数≥450×10^9/L、骨髓巨核细胞形态符合前纤维化/早期骨髓纤维化特征且不满足前纤维化/早期骨髓纤维化（pre-MF）次要诊断标准的患者，是否应将其归类为一种独立的MPN亚型——孤立性血小板增多症伴克隆性巨核细胞发育异常（clonal megakaryocyte dysplasia with isolated thrombocytosis, CMD-IT）。 结果：共有139名符合上述标准的受试者入组，本研究将其与原发性骨髓纤维化（primary myelofibrosis, PMF）患者进行对照，其中pre-MF患者402例、显性骨髓纤维化患者521例。CMD-IT患者中女性占比更高且年龄更轻。与PMF患者相比，CMD-IT患者的JAK2V617F突变频率更低（55% vs. 70%；[原文未明确标注具体P值]），CALR突变频率更高（37% vs. 17%；[原文未明确标注具体P值]），JAK2V617F易感位点JAK2 46/1的携带率更低（35% vs. 47%；p=0.021），且VEGFA rs3025039位点的等位基因频率更低（12% vs. 17%；p=0.030）。CMD-IT患者的血栓事件发生率低于pre-MF患者（9.7% vs. 26%；[原文未明确标注具体P值]）。 结论：本研究数据表明，CMD-IT是一种独立的MPN亚型，应纳入髓系肿瘤的分类体系。