Development of paroxysmal nocturnal hemoglobinuria in CALR-positive myeloproliferative neoplasm.
Development of paroxysmal nocturnal hemoglobinuria in CALR-positive myeloproliferative neoplasm.
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DOI：
10.2147/jbm.s103473
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发表时间：
2016
影响因子：
2
通讯作者：
Moliterno AR
中科院分区：
文献类型：
--
作者：
Fraiman YS;Cuka N;Batista D;Vuica-Ross M;Moliterno AR
阵发性睡眠性血红蛋白尿症（PNH）是一种以血管内溶血、血栓形成和骨髓衰竭为特征的疾病，与PIG-A基因突变相关，导致糖基磷脂酰肌醇锚定蛋白缺乏。关于PNH和PIG-A突变是否导致CD 55 −/CD 59 −细胞的内在存活益处或允许其在骨髓室中克隆扩增的外在容许环境，已经提出了许多假设。最近的数据已经确定了PIG-A突变与骨髓增生性疾病相关的其他基因突变的并发症，这表明PNH的一些表现是类似于其他骨髓增生异常或骨髓增生综合征的基因突变逐步进展的结果。我们在文献中首次报道了JAK 2 V617 F阴性、CALR阳性原发性血小板增多症患者发生具有临床意义的PNH，进一步支持了PNH的发生与多个基因突变的积累相关的假设，这些基因突变为克隆扩增创造了内在的生存益处。该病例研究还强调了基因组检测在诊断中的实用性以及对临床疾病进展的理解。
Paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by intravascular hemolysis, thrombosis, and bone marrow failure, is associated with mutations in the PIG-A gene, resulting in a deficiency of glycosylphosphatidylinositol-anchored proteins. Many hypotheses have been posed as to whether PNH and PIG-A mutations result in an intrinsic survival benefit of CD55−/CD59− cells or an extrinsic permissive environment that allows for their clonal expansion within the bone marrow compartment. Recent data have identified the concurrence of PIG-A mutations with additional genetic mutations associated with myeloproliferative disorders, suggesting that some presentations of PNH are the result of a stepwise progression of genetic mutations similar to other myelodysplastic or myeloproliferative syndromes. We report for the first time in the literature the development of clinically significant PNH in a patient with JAK2V617F-negative, CALR-positive essential thrombocythemia, providing further support to the hypothesis that the development of PNH is associated with the accumulation of multiple genetic mutations that create an intrinsic survival benefit for clonal expansion. This case study additionally highlights the utility of genomic testing in diagnosis and the understanding of disease progression in the clinical setting.