骨髓增殖性肿瘤患者巨核细胞病理特征及其与起始基因突变的相关性

OBJECTIVE: To investigate the pathological characteristics of megakaryocytes in myeloproliferative neoplasms （MPN）and their correlations with driver gene mutations. METHODS: Trephine specimens administered for 160 patients with MPN from February 2012 to October 2017 were reevaluated according to the World Health Organization（WHO）'s（2016）diagnostic criteria. RESULTS: This cohort of patients included 72（45.0％）men, with the median age of 59（range, 13–87）years, comprising 39 with polycythemia vera（PV）, 33 with essential thrombocythemia（ET）, 37 with prefibrotic/early-primary myelofibrosis（pre-PMF）, 37 with overt PMF, 1 with post-ET MF, 2 with post-PV MF, and 11 with MPN-unclassifiable（MPN-U）after the re-diagnosis. With PV, ET, pre-PMF, and overt PMF changes, proportions of dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes gradually increased, whereas erythropoiesis gradually decreased. Proportions of reticulin, collagen, and osteosclerosis grades of ≥1 also increased. Dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes were negatively correlated with erythropoiesis and positively correlated with granulopoiesis and fibrosis. In patients with pre- and overt PMF, dense clusters and naked nuclei of megakaryocytes were positively correlated with fibrosis. Patients with JAK2V617F MPN had significantly increased erythropoiesis（P＝0.022）. Patients with CALR-mutated MPN were characterized by increased loose and dense clusters; paratrabecular distribution and naked nuclei of megakaryocytes （P＝0.055, P＝0.002, P＝0.018, P＝0.008）; and increased reticulin, collagen, and osteosclerosis（P＝0.003, P<0.001, P＝0.001）. In patients with pre- and overt PMF, patients with JAK2V617F had increased cellularity（P＝0.037）. CALR-mutated patients had increased dense clusters and giant sizes of megakaryocytes, collagen, and osteosclerosis（P＝0.055, P＝0.059, P＝0.011, P＝0.046）. CONCLUSION: Megakaryocytes showed abnormal MPN morphology and distribution, which were related to fibrosis. CALR mutation was probably associated with abnormal morphology and distribution of megakaryocytes and fibrosis.