Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

SCIENTIFIC REPORTS — 2022 

Authors

Sánchez R., et al.

This study developed a DNA-based ultra-deep NGS method to detect BCR::ABL1 kinase domain mutations in CML and Ph+ ALL, supporting sensitive monitoring of therapy resistance. 

Topics

Hematologic malignancies · BCR::ABL1 leukemia · CML · Resistance monitoring · EVOseq

Expanded summary

This article focused on the detection of BCR::ABL1 kinase domain mutations, which are clinically relevant in cases of warning or treatment failure in chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. The study presented a DNA-based NGS approach for mutation detection and monitoring with 1.0E−4 sensitivity.

The method was validated against an established RNA-based nested NGS workflow. Across 129 patients and 162 samples, DNA-DeepNGS showed strong correlation with RNA-NestedNGS, with reported sensitivity of 92% and specificity of approximately 82%, including detection of mutations in low disease burden settings.

For Altum, this study supports capabilities in resistance mutation detection, clonal evolution and therapy monitoring, particularly where ultra-deep sequencing and robust bioinformatics are needed to detect clinically meaningful low-frequency variants. 

View article: https://doi.org/10.1038/s41598-022-17271-3