In Vitro Megakaryocyte Differentiation and Proplatelet Formation in Ph-Negative Classical Myeloproliferative Neoplasms: Distinct Patterns in the Different Clinical Phenotypes
In Vitro Megakaryocyte Differentiation and Proplatelet Formation in Ph-Negative Classical Myeloproliferative Neoplasms: Distinct Patterns in the Different Clinical Phenotypes
复制标题
DOI：
10.1371/journal.pone.0021015
复制
发表时间：
2011-06-15
期刊：
影响因子：
3.7
通讯作者：
Barosi, Giovanni
中科院分区：
文献类型：
--
作者：
Balduini, Alessandra;Badalucco, Stefania;Barosi, Giovanni
背景资料：Ph阴性骨髓增生性肿瘤（MPN）是一种克隆性疾病，包括原发性骨髓纤维化（PMF）、真性红细胞增多症（PV）和原发性血小板增多症（ET）。虽然MPN的发病机制还不完全清楚，巨核细胞谱系的参与是一个显着的feature.Methodology/主要结果：我们分析了在体外巨核细胞分化和proplatelet形成在30 PMF，8 ET，8 PV患者，和17名健康对照（CTRL）。在血小板生成素存在下，巨核细胞从外周血CD 34（+）或CD 45（+）细胞分化。MPN患者的巨核细胞输出量高于CTRL患者，与JAK 2 V617 F突变无关。PMF衍生的巨核细胞显示出球根状外观的细胞核，小于ET或PV衍生的巨核细胞，并形成呈现几种结构改变的前血小板。与此相反，ET-和PV-衍生的巨核细胞产生更多的proplatelets与显着增加的分叉和提示相比，控制和PMF。前血小板形成与患者外周血中的血小板计数相关。与纤维化前PMF的患者有巨核细胞增殖和前血小板形成的模式是类似的纤维化PMF和不同的ET。结论/意义：总之，MPN与高巨核细胞增殖潜力。巨核细胞形态和前血小板形成的显著差异将纤维化和纤维化前PMF与ET和PV区分开来。
Background: Ph-negative myeloproliferative neoplasms (MPNs) are clonal disorders that include primary myelofibrosis (PMF), polycythemia vera (PV) and essential thrombocythemia (ET). Although the pathogenesis of MPNs is still incompletely understood, an involvement of the megakaryocyte lineage is a distinctive feature.Methodology/Principal Findings: We analyzed the in vitro megakaryocyte differentiation and proplatelet formation in 30 PMF, 8 ET, 8 PV patients, and 17 healthy controls (CTRL). Megakaryocytes were differentiated from peripheral blood CD34(+) or CD45(+) cells in the presence of thrombopoietin. Megakaryocyte output was higher in MPN patients than in CTRL with no correlation with the JAK2 V617F mutation. PMF-derived megakaryocytes displayed nuclei with a bulbous appearance, were smaller than ET- or PV-derived megakaryocytes and formed proplatelets that presented several structural alterations. In contrast, ET- and PV-derived megakaryocytes produced more proplatelets with a striking increase in bifurcations and tips compared to both control and PMF. Proplatelets formation was correlated with platelet counts in patient peripheral blood. Patients with pre-fibrotic PMF had a pattern of megakaryocyte proliferation and proplatelet formation that was similar to that of fibrotic PMF and different from that of ET.Conclusions/Significance: In conclusion, MPNs are associated with high megakaryocyte proliferative potential. Profound differences in megakaryocyte morphology and proplatelet formation distinguish PMF, both fibrotic and prefibrotic, from ET and PV.