Next-Generation Sequencing and Detection of Minimal Residual Disease in Acute Myeloid Leukemia: Ready for Clinical Practice?

摘要: Acute myeloid leukemia (AML) represents a heterogeneous disease, both with respect to molecular pathogenesis and clinical outcome. Although dose-intensive chemotherapy allogeneic stem cell transplantation have improved outcomes in AML, there remains significant heterogeneity outcome such that approximately 20% of patients are cured existing therapies, therapy-refractory disease from the time diagnosis, 50% relapse die refractory after an initial response therapy.1-4 The challenge is how best determine prognosis identify which will substantive chance cure, likely or present disease. Current standard care uses clinical, cytogenetic, factors for risk stratification; however, pressing need better approaches prognostication AML. In recent years large sequencing studies AML identified spectrum recurrent somatic alterations contribute tumor initiation maintenance.5 Most importantly, this knowledge can be used improve stratification, prognostic algorithms incorporate focused profiling been developed validated patient cohorts.6-11 However, many questions remain regarding use practice other malignancies. First, value more extensive studies, as panels exome genome sequencing? Second, does intrapatient affect therapies? Third, most important, dynamic analysis during therapy inform prognosis? issue JAMA, Klco colleagues address these provide critical insight into role next-generation techniques context.12 authors analyzed diagnostic samples 71 de novo treated at single center integrative genomic including whole-genome whole-exome sequencing, RNA microRNA methylation arrays. were divided 3 groups: within first 6 months start therapy, those 12 months, remission than months. did not observe differences between groups numbers coding total mutations. Moreover, presence specific mutations sequence known novel genes, select noncoding mutations, was associated concluded done point (eg, diagnosis) sufficiently predict important limitations accuracy robustness models based on profiling,13 relatively small, single-institution cohort, recognized by authors, factor significantly limits their ability tool It perform similar, high-quality larger cohorts, ideally multicenter trials homogeneous therapeutic approach, ascertain whether state-of-the-art diagnosis current schema limited mutational cytogenetic analyses, parameters. also sought previously unanswered question: Can serial AML? 2 different enhanced high-coverage genes banked targeted, short amplicon platform preserved paraffin. This allowed investigators accurately quantitatively follow burden before, during, cohort. platforms assess morphologic complete clearance (variant allele frequency ≤2.5%) relationship responses outcomes. assessed 50 day 30, them patients. One group (26 patients) showed eradication detected sample remission. By contrast, second (24 retained least 1 mutation diagnosRelated article page 811 Opinion