ArticleHaematologica2016
Ultra-deep sequencing leads to earlier and more sensitive detection of the tyrosine kinase inhibitor resistance mutation T315I in chronic myeloid leukemia.
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 54 citations in OpenAlex.
- Chronic myeloid leukemia: incorporation of recent advances into current treatment algorithms.Blood cancer journal · 2026Review
- Evolving Therapeutic Algorithms in Chronic Myeloid Leukemia: Integrating Efficacy, Safety, and Survivorship.Biomedicines · 2026Review
- Chronic Myeloid Leukemia and the T315IInternational journal of molecular sciences · 2025Review
- A nomogram for predicting T315I-free survival in chronic phase chronic myeloid leukemia patients: a multicenter retrospective study.Scientific reports · 2025Article
- From Detection to Cure - Emerging Roles for Urinary Tumor DNA (utDNA) in Bladder Cancer.Current oncology reports · 2024Review
- Validation of a novel NGS based BCR::ABL1 kinase domain mutation detection assay in Indian cohort.Scientific reports · 2024Article
- Therapeutic options for chronic myeloid leukemia following the failure of second-generation tyrosine kinase inhibitor therapy.Frontiers in oncology · 2024Review
- Case report: Selpercatinib in the treatment ofFrontiers in oncology · 2024Article
- Resistance mutations in CML and how we approach them.Hematology. American Society of Hematology. Education Program · 2023Review
- European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia.Leukemia · 2023Review
- Sequence-Based Platforms for Discovering Biomarkers in Liquid Biopsy of Non-Small-Cell Lung Cancer.Cancers · 2023Review
- Clinical Circulating Tumor DNA Testing for Precision Oncology.Cancer research and treatment · 2023Article
- Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer.Exploration of targeted anti-tumor therapy · 2023Review
- Article
- Current and Future Perspectives of Cell-Free DNA in Liquid Biopsy.Current issues in molecular biology · 2022Review
- Overcoming Resistance to Kinase Inhibitors: The Paradigm of Chronic Myeloid Leukemia.OncoTargets and therapy · 2022Review
- A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study.Frontiers in oncology · 2022Article
- Article
- Molecular Testing in CML between Old and New Methods: Are We at a Turning Point?Journal of clinical medicine · 2020Review
- Chronic Myeloid Leukemia Prognosis and Therapy: Criticisms and Perspectives.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic myeloid leukemia cells acquire resistance to tyrosine kinase inhibitors through mutations in the ABL1 kinase domain. The T315I mutation mediates resistance to imatinib, dasatinib, nilotinib and bosutinib, whereas sensitivity to ponatinib remains. Mutation detection by conventional Sanger sequencing requires 10%-20% expansion of the mutated subclone. We studied the T315I mutation development by ultra-deep sequencing on the 454 XL+ platform (Roche) in comparison to Sanger sequencing. By ultra-deep sequencing, mutations were detected at loads of 1%-2%. We selected 40 patients who had failed first-line to third-line treatment (imatinib, dasatinib, nilotinib) and had high loads of the T315I mutation detected by Sanger sequencing. We confirmed T315I mutations by ultra-deep sequencing and investigated the mutation dynamics by backtracking earlier samples. In 20 of 40 patients, we identified the T315I three months (median) before Sanger sequencing detection limits were reached. To exclude sporadic low percentage mutation development without subsequent mutation outgrowth, we selected 42 patients without resistance mutations detected by Sanger sequencing but loss of major molecular response. Here, no mutation was detected by ultradeep sequencing. Additional non-T315I resistance mutations were found in 20 of 40 patients. Only 15% had two mutations per cell; the other cases showed multiple independently mutated clones and the T315I clone demonstrated a rapid outgrowth. In conclusion, T315I mutations could be detected earlier by ultra-deep sequencing compared to Sanger sequencing in a selected group of cases. Earlier mutation detection by ultra-deep sequencing might allow treatment to be changed before clonal increase of cells with the T315I mutation.
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