Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones
Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones
复制标题
DOI：
10.1046/j.1365-2141.2001.03191.x
复制
发表时间：
2001-12-01
影响因子：
6.5
通讯作者：
Young, NS
中科院分区：
文献类型：
--
作者：
Maciejewski, JP;Rivera, C;Young, NS
由于 Ham 试验不敏感，阵发性睡眠性血红蛋白尿 (PNH) 被错误地视为再生障碍性贫血 (AA) 的晚期克隆性并发症。为了阐明 PNH 和骨髓衰竭之间的关系，我们在大量 AA、骨髓增生异常 (MDS) 和纯溶血性 PNH 患者中检测了糖基磷脂酰锚定蛋白缺陷 (GPI-AP) 粒细胞的存在情况。在 32% 的新 AA 患者和 18% 的 MDS 患者中检测到 PNH 克隆。在系列研究中，这一比例在诊断后 15 年内都没有变化，这表明异常细胞的扩增是一个早期事件（即在初次出现之前）。对于所有具有 PNH 克隆的患者，平均在就诊时发现了 14% 的 PNH 粒细胞，在 10 年时发现了 37%。患有 PNH 但没有血细胞减少症的患者比患有 AA/PNH 综合征的患者表现出更高的 GPI-AP 缺陷细胞百分比。免疫抑制后，PNH克隆对造血的贡献没有变化，反驳了PNH中的“免疫逃逸”理论。临床上，高比例的 GPI-AP 缺陷细胞与骨髓细胞增多相关。 GPI-AP 缺陷细胞在有和没有核型异常的患者中相似地存在。我们的结果表明，GPI-AP 缺陷克隆在经典溶血性 PNH 和伴有骨髓衰竭的 PNH 之间表现出定量和动力学差异，其中在病程后期进化率较低。
Because of the Insensitivity of the Ham test, paroxysmal nocturnal haemoglobinuria (PNH) has been inaccurately viewed as a late clonal complication of aplastic anaemia (AA). To clarify the relationship between PNH and marrow failure, we tested for the presence of glycosylphosphatidyl-anchored protein-deficient (GPI-AP) granulocytes in large cohorts of patients with AA, myelodysplasia (MDS), and pure haemolytic PNH. A PNH clone was detected in 32% of new AA patients and 18% of MDS patients. In serial studies, this proportion did not change up to 15 years after diagnosis, suggesting that expansion of aberrant cells is an early event (i.e. prior to initial presentation). For all patients with a PNH clone, on average 14% of PNH granulocytes were found on presentation and 37% at 10 years. Patients with PNH but without cytopenia showed higher percentages of GPI-AP-deficient cells than did those with the AA/PNH syndrome. After immunosuppression, there was no change in the contribution of PNH clone to blood production, arguing against the 'immune-escape' theory in PNH. Clinically, a high proportion of GPI-AP-deficient cells correlated with marrow hypercellularity. GPI-AP-deficient cells were similarly present in patients with and without karyotypic abnormalities. Our results indicate that the GPI-AP-deficient clones show quantitative and kinetic differences between classic haemolytic PNH and PNH with marrow failure, in which the evolution rate is low later in the course of the disease.