Ultra-Accurate Assessment of Pretreatment ABL1 Kinase Domain (KD) Mutations in Patients (pts) with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Using Duplex Sequencing (DS)

Background: Some previous studies in Ph+ ALL suggested that T315I mutations of the ABL1 KD are present in many pts prior to tyrosine kinase inhibitor (TKI) treatment. However, these reports used RT-PCR to generate complementary DNA (cDNA) prior to analysis, which may introduce random errors and lead to false positive results. We hypothesized that ultrasensitive DS of genomic DNA (gDNA) would more accurately detect low-level pretreatment ABL1 mutations in Ph+ ALL because it does not rely upon error prone RT-PCR.