Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes
Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes
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DOI：
10.1182/blood-2015-03-631747
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发表时间：
2015-07-02
期刊：
影响因子：
20.3
通讯作者：
Ebert, Benjamin L.
中科院分区：
文献类型：
--
作者：
Steensma, David P.;Bejar, Rafael;Ebert, Benjamin L.
最近对大规模人群的遗传分析表明，造血细胞中导致克隆扩增的体细胞突变通常在人类衰老过程中获得。克隆限制性造血与随后诊断为骨髓或淋巴瘤的风险增加以及全因死亡率增加相关。虽然骨髓增生异常综合征（MDS）的定义是血细胞减少，异常形态的血液和骨髓细胞，克隆造血，大多数人谁获得克隆造血在衰老过程中将永远不会发展MDS。因此，在没有血细胞减少和发育不良造血的情况下获得驱动克隆扩增的体细胞突变可以被认为是不确定潜能的克隆造血（CHIP），类似于意义不明的单克隆丙种球蛋白病和单克隆B细胞淋巴细胞增多症，这是血液肿瘤的前驱状态，但通常是良性的，不会进展。由于突变经常在健康老年人中观察到，在没有其他MDS证据的血细胞减少患者中检测MDS相关体细胞突变可能会导致诊断不确定性。在这里，我们讨论了CHIP的性质和患病率，这种状态与MDS的区别，以及目前关于骨髓恶性肿瘤诊断标准的不确定性。
Recent genetic analyses of large populations have revealed that somatic mutations in hematopoietic cells leading to clonal expansion are commonly acquired during human aging. Clonally restricted hematopoiesis is associated with an increased risk of subsequent diagnosis of myeloid or lymphoid neoplasia and increased all-cause mortality. Although myelodysplastic syndromes (MDS) are defined by cytopenias, dysplastic morphology of blood and marrow cells, and clonal hematopoiesis, most individuals who acquire clonal hematopoiesis during aging will never develop MDS. Therefore, acquisition of somatic mutations that drive clonal expansion in the absence of cytopenias and dysplastic hematopoiesis can be considered clonal hematopoiesis of indeterminate potential (CHIP), analogous to monoclonal gammopathy of undetermined significance and monoclonal B-cell lymphocytosis, which are precursor states for hematologic neoplasms but are usually benign and do not progress. Because mutations are frequently observed in healthy older persons, detection of an MDS-associated somatic mutation in a cytopenic patient without other evidence of MDS may cause diagnostic uncertainty. Here we discuss the nature and prevalence of CHIP, distinction of this state from MDS, and current areas of uncertainty regarding diagnostic criteria for myeloid malignancies.