Eryptosis in polycythemia vera and essential thrombocythemia

POSTEPY HIGIENY I MEDYCYNY DOSWIADCZALNEJ(2020)

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摘要
Aim: Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia-negative myelo-proliferative neoplasms with documented apoptosis impairment at the level of hematopoietic stem cell. However, so far no study has evaluated apoptosis of circulating blood neoplastic cells, including the suicidal death of erythrocytes - eryptosis. Material/Methods: Erythrocytes from 61 patients (24 PV and 37 ET) naive to and treated with hydroxyurea (HU) and 13 healthy individuals were analysed using flow cytometry to quantify phosphatidylserine (PS) externalization from Annexin-V-binding, calpain activity from 7-amino-4-chloromethylcoumarin (CMAC)-fluorescence, cell volume from forward scattered light (FSC) and cell shape from side scattered light (SSC). Results: Significantly increased levels of calpain activity and PS exposure were observed in both ET and PV naive patients, indicating enhanced eryptosis. Among HU-treated patients, a significant increase in calpain activity in the ET group and a decrease in the PV group were observed compared to patients without cytoreductive therapy. Among PV patients, FSC was substantially higher in the HU-treated group than in the naive group, whereas no significant differences were found between HU-treated and HU-nave groups of ET patients. Conclusions: The enhanced eryptosis in ET and PV patients may be a form of systemic compensation of the pathological bone marrow overproduction of erythrocytes. HU, the basic cytoreductive drug used in ET and PV, may affect eryptosis in PV and ET in different ways depending on disease. The JAK2V617F mutation was not observed to have any effect on eryptosis in ET.
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关键词
Essential thrombocythemia,Polycythemia vera,Eryptosis,Hydroxyurea,JAK2V617F mutation
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