Mutation analysis of BCR-ABL1 kinase domain in chronic myeloid leukemia patients with tyrosine kinase inhibitors resistance: a Malaysian cohort study

• Published in: BMC Research Notes
• Main Author: Seman Z.A.; Ahid F.; Kamaluddin N.R.; Sahid E.N.M.; Esa E.; Said S.S.M.; Azman N.; Mat W.K.D.W.; Abdullah J.; Ali N.A.; Khalid M.K.N.M.; Yusoff Y.M.
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85191066262&doi=10.1186%2fs13104-024-06772-1&partnerID=40&md5=16f88fbdbffb24943a32696ab1a72323

Objective: Mutational analysis of BCR::ABL1 kinase domain (KD) is a crucial component of clinical decision algorithms for chronic myeloid leukemia (CML) patients with failure or warning responses to tyrosine kinase inhibitor (TKI) therapy. This study aimed to detect BCR::ABL1 KD mutations in CML patients with treatment resistance and assess the concordance between NGS (next generation sequencing) and Sanger sequencing (SS) in detecting these mutations. Results: In total, 12 different BCR::ABL1 KD mutations were identified by SS in 22.6% (19/84) of patients who were resistant to TKI treatment. Interestingly, NGS analysis of the same patient group revealed an additional four different BCR::ABL1 KD mutations in 27.4% (23/84) of patients. These mutations are M244V, A344V, E355A, and E459K with variant read frequency below 15%. No mutation was detected in 18 patients with optimal response to TKI therapy. Resistance to TKIs is associated with the acquisition of additional mutations in BCR::ABL1 KD after treatment with TKIs. Additionally, the use of NGS is advised for accurately determining the mutation status of BCR::ABL1 KD, particularly in cases where the allele frequency is low, and for identifying mutations across multiple exons simultaneously. Therefore, the utilization of NGS as a diagnostic platform for this test is very promising to guide therapeutic decision-making. © The Author(s) 2024.