文章：

慢性自然杀伤细胞淋巴细胞增殖性疾病的体细胞突变高清图谱

A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics

原文发布日期：2020-04-24

DOI: 10.1038/s41408-020-0308-3

类型: Article

开放获取: 是

英文摘要：

BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12–84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P ≤ 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15–60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1-like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL.
 

摘要翻译： 

BCR-ABL1样B细胞前体急性淋巴细胞白血病（BCP-ALL）在成人中的特征仍未明确。我们试图通过新型RNA测序标志，在一系列BCP-ALL患者中确定青少年和成人BCR-ABL1样ALL的发生频率及预后。为此，我们在100例经风险适应性ALL临床试验治疗的BCP-ALL患者队列中，开发并测试了包含42个与BCR-ABL1样特征相关基因的RNA测序定制面板。通过二代测序技术对33个基因组成的面板中与BCR-ABL1样ALL相关的突变进行了研究，同时分析了CRLF2过表达以及IKZF1/CDKN2A/B缺失。基于热图聚类分析，79例患者（12-84岁）中有20例（25%）被归类为BCR-ABL1样，其中ENAM、IGJ和CRLF2显著过表达（P≤0.001）。在15-60岁患者中，BCR-ABL1样亚型占比达29%，其分子特征包括：CRLF2过表达（75%病例）、IKZF1缺失（64%）、CDKN2A/B缺失（57%）和JAK2突变（57%）。在诱导治疗后达到微小残留病阴性的患者中，携带BCR-ABL1样ALL特征者与非BCR-ABL1样患者相比，具有更高的复发率和更短完全缓解持续时间（P=0.007）。由此，我们鉴定出一种与成人ALL患者不良预后相关的BCR-ABL1样ALL新型分子标志。

原文链接：

A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics