Subclonal NT5C2 mutations are associated with poor outcomes after relapse of pediatric acute lymphoblastic leukemia
Subclonal NT5C2 mutations are associated with poor outcomes after relapse of pediatric acute lymphoblastic leukemia
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DOI：
10.1182/blood.2019002499
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发表时间：
2020-03-19
期刊：
影响因子：
20.3
通讯作者：
Kirschner-Schwabe, Renate
中科院分区：
文献类型：
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作者：
Barz, Malwine J.;Hof, Jana;Kirschner-Schwabe, Renate
细胞溶质59-核苷酸酶II（NT 5C 2）的激活突变被认为是通过赋予嘌呤类似物耐药性而驱动急性淋巴细胞白血病（ALL）复发的原因。为了检测NT 5C 2突变在复发性ALL中的临床作用，我们使用测序和敏感的等位基因特异性实时聚合酶链反应分析了455例在ALL-REZ BFM 2002复发试验中接受治疗的复发性前体B细胞ALL患者的NT 5C 2。我们在455例B细胞前体ALL复发患者中的75例（16.5%）中检测到110个NT 5C 2突变。三分之二的复发携带亚克隆突变，只有三分之一携带克隆突变。复发后有克隆和亚克隆NT 5C 2突变的患者的无事件生存率低于无突变的患者（19%和25% vs 53%，P
Activating mutations in cytosolic 59-nucleotidase II (NT5C2) are considered to drive relapse formation in acute lymphoblastic leukemia (ALL) by conferring purine analog resistance. To examine the clinical effects of NT5C2 mutations in relapsed ALL, we analyzed NT5C2 in 455 relapsed B-cell precursor ALL patients treated within the ALL-REZ BFM 2002 relapse trial using sequencing and sensitive allele-specific real-time polymerase chain reaction. We detected 110 NT5C2 mutations in 75 (16.5%) of 455 B-cell precursor ALL relapses. Two-thirds of relapses harbored subclonal mutations and only one-third harbored clonal mutations. Event-free survival after relapse was inferior in patients with relapses with clonal and subclonal NT5C2 mutations compared with those without (19% and 25% vs 53%, P