Apoptosis resistance of blood cells from patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome
Apoptosis resistance of blood cells from patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome
复制标题
DOI：
10.1182/blood.v90.7.2716.2716_2716_2722
复制
发表时间：
1997-10-01
期刊：
影响因子：
20.3
通讯作者：
Takatsuki, K
中科院分区：
文献类型：
--
作者：
Horikawa, K;Nakakuma, H;Takatsuki, K
骨髓（BM）发育不良是阵发性睡眠性血红蛋白尿症（PNH）的主要死因。然而，很少有人知道的分子事件导致发育不全。考虑到PNH和再生障碍性贫血（AA）之间的密切病理联系，建议在其BM衰竭的发展中有类似的机制。最近的报告表明，在AA中，骨髓增生介导的BM抑制。因此可以想象，细胞凋亡也会导致PNH中的BM发育不全，如果是这种情况，PNH克隆需要在细胞凋亡中存活并显示出相当大的扩增，从而导致临床表现。我们在这里报告，从11例PNH患者获得的粒细胞明显低于20例健康人的敏感性，无论是自发凋亡没有任何配体和诱导的抗FAS（CD 95）抗体在体外。患者骨髓CD_（34）~+细胞对肿瘤坏死因子-α、干扰素-γ及抗FAS抗体诱导的细胞凋亡也有抵抗性。淋巴细胞的病理抵抗与固有的细胞凋亡抵抗无明显区别。13例AA患者和12例骨髓增生异常综合征（MDS）患者的粒细胞表现出类似的抗凋亡。MDS-BM的CD 34（+）细胞也有类似的趋势。因此，对细胞凋亡的相对抗性支持细胞凋亡在PNH和相关干细胞疾病的骨髓损伤中的致病意义。(C)1997年，美国血液学会。
Bone marrow (BM) hypoplasia is a major cause of death in paroxysmal nocturnal hemoglobinuria (PNH). However, little is known about the molecular events leading to the hypoplasia. Considering the close pathologic association between PNH and aplastic anemia (AA), it is suggested that a similar mechanism operates in the development of their BM failure. Recent reports have indicated apoptosis-mediated BM suppression in AA. It is thus conceivable that apoptosis also operates to cause BM hypoplasia in PNH, if this is the case, PNH clones need to survive apoptosis and show considerable expansion leading to clinical manifestations. We report here that granulocytes obtained from 11 patients with PNH were apparently less susceptible than those from 20 healthy individuals to both spontaneous apoptosis without any ligands and that induced by anti-FAS (CD95) antibody in vitro. The patients' BM CD34(+) cells were also resistant to apoptosis induced by treatment with tumor necrosis factor-alpha, interferon-gamma, and subsequently with anti FAS antibody, In lymphocytes, the pathologic resistance was not discriminated from inherent resistance to apoptosis. Granulocytes from 13 patients with AA and 12 patients with myelodysplastic syndrome (MDS) exhibited similar resistance to apoptosis. CD34(+) cells from MDS-BM also showed similar tendency. Thus, the comparative resistance to apoptosis supports the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders. (C) 1997 by The American Society of Hematology.