Journal
CANCERS
Volume 14, Issue 24, Pages -Publisher
MDPI
DOI: 10.3390/cancers14246205
Keywords
acute myeloid leukemia; IDH1; 2 mutation; measurable residual disease; NPM1 mutation; locked nucleic acid quantitative PCR
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The study demonstrates the potential of LNA-qPCR for monitoring IDH1/2 mutations MRD in AML by correlating with NPM1 qPCR MRD and predicting relapse risk.
Simple Summary Measurable residual disease (MRD) monitoring is crucial in managing AML to predict the risk of relapse. A better understanding of which MRD technique and molecular target will have an effective clinical impact on AML is still required. Locked nucleic acid quantitative Real-Time PCR assay (LNA-qPCR) is sensitive and specific for quantifying oncogenetic single-nucleotide variation. We assessed the role of LNA-qPCR in the monitoring of IDH1/2 mutations MRD in eighty-eight AML patients from multiple centers. We found that IDH1/2 LNA-qPCR MRD correlates well with NPM1 qPCR MRD, predicts relapse-free survival and cumulative incidence of relapse, and is a potential MRD technique for IDH1/2-mutated AML patients with reduced IDH1/2 mutant levels after complete remission. Locked nucleic acid quantitative Real-Time PCR (LNA-qPCR) for IDH1/2 mutations in AML measurable residual disease (MRD) detection is rarely reported. LNA-qPCR was applied to quantify IDH1/2 mutants MRD kinetics in bone marrow from 88 IDH1/2-mutated AML patients, and correlated with NPM1-MRD, clinical characteristics, and outcomes. The median normalized copy number (NCN) of IDH1/2 mutants decreased significantly from 53,228 (range 87-980,686)/ALB x 10(6) at diagnosis to 773 (range 1.5-103,600)/ALB x 10(6) at first complete remission (CR). IDH1/2 LNA-qPCR MRD was concordant with remission status or NPM1-MRD in 79.5% (70/88) of patients. Younger patients and patients with FLT3 mutations had higher concordance. The Spearman correlation coefficient (r(s)) and concordance rate between the log reduction of IDH1/2 LNA-qPCR and NPM1-MRD were 0.68 and 81% (K = 0.63, 95% CI 0.50-0.74), respectively. IDH1/2-MRD > 2 log reduction at first CR predicted significantly better relapse-free survival (3-year RFS rates 52.9% vs. 31.9%, p = 0.007) and cumulative incidence of relapse (3-year CIR rates 44.5% vs. 64.5%, p = 0.012) compared to IDH1/2-MRD <= 2 log reduction. IDH1/2-MRD > 2 log reduction during consolidation is also associated with a significantly lower CIR rate than IDH1/2-MRD <= 2 log reduction (3-year CIR rates 42.3% vs. 68.8%, p = 0.019). LNA-qPCR for IDH1/2 mutation is a potential MRD technique to predict relapse in IDH1/2-mutated AML patients, especially for those with IDH1/2 MRD > 2 log reduction at first CR or a concurrent FLT3 mutation.
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