Additional Chromosome Abnormalities, BCR-ABL Tyrosine Kinase Domain Mutations and Clinical Outcome in Hungarian Tyrosine Kinase Inhibitor-Resistant Chronic Myelogenous Leukemia Patients
| Autor: | Andrea Sipos, Sandor Lueff, Árpád Bátai, Anikó Barta, András Bors, András Kozma, Péter Reményi, Emma Ádám, Attila Tordai, Hajnalka Andrikovics, Gabriella Halm, György Ujj, Sarolta Nahajevszky, Nóra Meggyesi, Sandor Fekete, Tamas Masszi |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Adolescent medicine.drug_class Fusion Proteins bcr-abl medicine.disease_cause Disease-Free Survival Tyrosine-kinase inhibitor Myelogenous Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases medicine Humans Point Mutation CD135 Child Protein Kinase Inhibitors neoplasms Aged Chromosome Aberrations Hungary Mutation ABL AXL receptor tyrosine kinase business.industry Hematology General Medicine Middle Aged Protein-Tyrosine Kinases medicine.disease Protein Structure Tertiary Survival Rate Drug Resistance Neoplasm Case-Control Studies Cancer research Female business Tyrosine kinase Chronic myelogenous leukemia |
| Zdroj: | Acta Haematologica. 127:34-42 |
| ISSN: | 1421-9662 0001-5792 |
| Popis: | Background: Additional chromosome abnormalities (ACAs), mutations of the BCR-ABL tyrosine kinase domain (TKD) and BCR-ABL splice variants may cause resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myelogenous leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoid leukemia (ALL). Methods: Karyotyping and BCR-ABL TKD mutation screening were performed in 71 imatinib-resistant CML patients and 6 Ph+ ALL patients. A total of 56 out of these 77 patients received second-generation TKI. Results: ACAs were present in 30 of 65 imatinib-resistant patients (46%). In 27 of 74 imatinib-resistant patients (36%), 15 different BCR-ABL TKD mutations were detected. Mutations were found in 25% of chronic-phase patients (12/47), 33% of accelerated-phase patients (5/15), 71% of blast crisis CML patients (5/7) and 100% of ALL patients. In nilotinib-resistant patients, Y253H, T315I and F359I/V mutations were detected; in dasatinib-resistant patients, L248M, E279K and T315I mutations were detected. T315I was found more frequently in patients on dasatinib than on imatinib therapy. The presence of ACAs predicted shorter survival during first- and second-generation TKI therapy, while TKD mutations only influenced survival during second-generation TKI therapy. Conclusion: For patients with TKI resistance, mutation and ACA screening may play a role in identifying patients with poorer prognosis. |
| Databáze: | OpenAIRE |
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