Department of Pediatrics, Perlmutter Cancer Center, NYU Langone Health, New York.
Department of Pathology, Perlmutter Cancer Center, NYU Langone Health, New York.
Pediatr Blood Cancer. 2020 Jul;67(7):e28306. doi: 10.1002/pbc.28306. Epub 2020 May 11.
Relapse-enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet-based polymerase chain reaction to establish whether relapse-enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.
复发富集的体细胞变异驱动儿童急性淋巴细胞白血病的耐药性。我们使用基于数字微滴的聚合酶链反应来确定在明显复发之前，外周血样本中是否可以检测到新兴亚克隆中的复发富集突变。尽管某些探针的灵敏度有限，阻碍了某些变体的检测，但我们成功地以 0.005%至 0.3%的分数丰度检测到了 NT5C2 和 PRPS1 中的变体，比复发提前了 41 至 116 天。由于这两个基因的突变赋予了对硫嘌呤的耐药性，因此可以使用外周血进行早期检测方案，在明显复发前改变维持治疗以消灭耐药克隆。
