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Measuring minimal residual disease in acute myeloid leukemia with MASQ

ABSTRACT: Measuring minimal residual disease (MRD) in cancer has clinical applications for prognosis, monitoring treatment, and detection of recurrence. Simple sequence-based methods to detect nucleotide substitution variants have error rates (about 10^-3) that limit sensitive detection. We developed and characterize the performance of MASQ (Multiplex Accurate Sensitive Quantitation), a method with an error rate on the order of 10^-6. MASQ counts variant templates accurately in the presence of millions of host genomes by using tags to identify each template and demanding consensus over multiple reads of each template. At least 50 target loci can be multiplexed and quantified accurately over a wide range of genomic DNA input amounts. Simultaneously assaying many target variants allows for efficient use of sample, high sensitivity, robustness, and the ability to distinguish subpopulations of variants. We tested MASQ in a small pilot study measuring residual disease in acute myeloid leukemia (AML) patients who entered remission following induction therapy. We detect leukemic variants in the blood and bone marrow samples of all five patients, after induction therapy. We observe evidence of subclonal structure following treatment and find higher target variant frequencies in patients who go on to relapse.

PROVIDER: EGAS00001003732 | EGA |

REPOSITORIES: EGA

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