signature=1c8d2dcd7a2ea3070412e7a02e16ca14,CEBPA–double-mutated acute myeloid leukemia displays a un...-优快云博客

CEBPA基因突变在约5%-10%的急性髓系白血病病例中发生，且双突变通常与较好的临床预后相关。研究发现，CEBPA双突变患者在所有细胞群中表现出常见的表型异常，这些异常依赖于CEBPA双突变的多系参与。通过细胞分选后的突变分析，确定了这种共同的表型特征。通过多维度分析表型数据，开发了一种包括10个核心参数的分类器，能够在幼稚和成熟骨髓细胞群中准确区分CEBPA双突变病例。此方法在独立中心的验证集中展现出100%的特异性和敏感性，为CEBPA双突变状态的大规模早期检测提供了一种可靠的方法，允许在选定病例中进行基因测序聚焦。

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摘要：

Mutations in CCAAT/enhancer binding protein α (CEBPA) occur in 5–10% of cases of acute myeloid leukemia.CEBPA-double-mutated cases usually bear biallelic N- and C-terminal mutations and are associated with a favorable clinical outcome. Identification ofCEBPAmutants is challenging because of the variety of mutations, intrinsic characteristics of the gene and technical issues. Several screening methods (fragment-length analysis, gene expression array) have been proposed especially for large-scale clinical use; although efficient, they are limited by specific concerns. We investigated the phenotypic profile of blast and maturing bone marrow cell compartments at diagnosis in 251 cases of acute myeloid leukemia. In this cohort, 16 (6.4%) patients had twoCEBPAmutations, whereas ten (4.0%) had a single mutation. First, we highlighted that theCEBPA-double-mutated subset displays recurrent phenotypic abnormalities in all cell compartments. By mutational analysis after cell sorting, we demonstrated that this common phenotypic signature depends onCEBPA-double-mutated multi-lineage involvement. From a multidimensional study of phenotypic data, we developed a classifier including ten core and widely available parameters. The selected markers on blasts (CD34, CD117, CD7, CD15, CD65), neutrophil (SSC, CD64), monocytic (CD14, CD64) and erythroid (CD117) compartments were able to clusterCEBPA-double-mutated cases. In a validation set of 259 AML cases from three independent centers, our classifier showed excellent performance with 100% specificity and 100% sensitivity. We have, therefore, established a reliable screening method, based upon multidimensional analysis of widely available phenotypic parameters. This method provides early results and is suitable for large-scale detection ofCEBPA-double-mutated status, allowing gene sequencing to be focused in selected cases.

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