Elevated extracellular trap formation and contact system activation in acute leukemia
Elevated extracellular trap formation and contact system activation in acute leukemia
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DOI：
10.1007/s11239-018-1713-3
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发表时间：
2018-10-01
影响因子：
4
通讯作者：
Kim, Hyun Kyung
中科院分区：
文献类型：
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作者：
Kim, Tae Yeul;Gu, Ja-Yoon;Kim, Hyun Kyung
白血病细胞在激活时将其核内容物释放到细胞外间隙。释放的核内容称为细胞外陷阱，可以激活凝血接触系统。这项研究评估了包括急性白血病在内的恶性血液病患者接触系统激活的程度、细胞外陷阱水平和凝血活性。对154例恶性血液病患者(急性白血病29例，骨髓增生异常综合征20例，骨髓增殖性肿瘤69例，浆细胞性骨髓瘤36例)和48例正常人的凝血因子(纤维蛋白原、凝血因子VII、VIII、IX、XII)、D-二聚体、凝血酶生成、细胞外TRAP标志物(组蛋白-DNA复合体、游离dsDNA、白细胞弹性蛋白酶)和接触系统标志物(激活因子XIIa、高分子激肽原、前激肽释放酶、缓激肽)进行了检测。急性白血病患者的峰值凝血酶、细胞外TRAP标志物和凝血因子XIIa水平最高。XIIa因子水平与急性白血病的发生显著相关。组蛋白-DNA复合体和无细胞dsDNA是与凝血因子XIIa水平显著相关的因素。3个细胞外陷阱标志物和2个凝血酶生成标志物在恶性血液病的止血异常中起重要作用。接触系统在急性白血病中被激活，其激活程度与细胞外陷阱的形成程度密切相关。这一发现表明，细胞外陷阱可能是接触系统激活的主要来源，针对细胞外陷阱形成或接触系统激活的治疗策略可能对急性白血病有利。
Leukemic cells release their nuclear contents into the extracellular space upon activation. The released nuclear contents, called extracellular traps, can activate the contact system of coagulation. This study accessed the extent of contact system activation, the levels of extracellular traps, and coagulation activation in hematologic malignancies including acute leukemia. In 154 patients with hematologic malignancies (acute leukemia, n = 29; myelodysplastic syndrome, n= 20; myeloproliferative neoplasms, n = 69; plasma cell myeloma, n = 36) and 48 normal controls, the levels of coagulation factors (fibrinogen and factor VII, VIII, IX, and XII), D-dimer, thrombin generation, extracellular trap markers (histone-DNA complex, cell-free dsDNA, leukocyte elastase), and contact system markers (activated factor XII [XIIa], high-molecular-weight kininogen, prekallikrein, bradykinin) were measured. Patients with acute leukemia showed the highest levels of peak thrombin, extracellular trap markers, and factor XIIa. Factor XIIa level was significantly associated with the presence of acute leukemia. The histone-DNA complex and cell-free dsDNA were revealed as significant associated factors with the factor XIIa level. Three markers of extracellular traps and two markers of thrombin generation significantly contributed to the hemostatic abnormalities in hematologic malignancies. Contact system was activated in acute leukemia and its activation was significantly associated with the extent of extracellular trap formation. This finding suggests that extracellular traps might be a major source of contact system activation and therapeutic strategies targeting extracellular trap formation or contact system activation may be beneficial in acute leukemia.