Targeted Next-Generation Sequencing Identifies Additional Mutations Other than BCR∷ABL in Chronic Myeloid Leukemia Patients: A Chinese Monocentric Retrospective Study

Abstract

A proportion of patients with somatic variants show resistance or intolerance to TKI therapy, indicating additional mutations other than BCR∷ABL1 may lead to TKI treatment failure or disease progression. We retrospectively evaluated 151 CML patients receiving TKI therapy and performed next-generation sequencing (NGS) analysis of 22 CML patients at diagnosis to explore the mutation spectrum other than BCR∷ABL1 affecting the achievement of molecular responses. The most frequently mutated gene was ASXL1 (40.9%). NOTCH3 and RELN mutations were only carried by subjects failing to achieve a major molecular response (MMR) at 12 months. The distribution frequency of ASXL1 mutations was higher in the group that did not achieve MR4.0 at 36 months (p = 0.023). The achievement of MR4.5 at 12 months was adversely impacted by the presence of >2 gene mutations (p = 0.024). In the analysis of clinical characteristics, hemoglobin concentration (HB) and MMR were independent factors for deep molecular response (DMR), and initial 2GTKI therapy was better than 1GTKI in the achievement of molecular response. For the scoring system, we found the ELTS score was the best for predicting the efficacy of TKI therapy and the Socal score was the best for predicting mutations other than BCR∷ABL.