Structural modeling of V299L and E459K Bcr-Abl mutation, and sequential therapy of tyrosine kinase inhibitors for the compound mutations
| Autor: | Il-Young Kweon, Soo-Hyun Kim, Dong-Wook Kim, Nam Doo Kim, Wan-Seok Kim, Sa-Hee Park, Dongho Kim, Jeong Hyeok Yoon, Jeong Lee, Hyun-Gyung Goh, Haarin Chun, Byung-Sik Cho |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Cancer Research medicine.drug_class Fusion Proteins bcr-abl Antineoplastic Agents Biology medicine.disease_cause Polymerase Chain Reaction Piperazines Tyrosine-kinase inhibitor Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases medicine Humans RNA Messenger Protein Kinase Inhibitors Mutation Myeloid leukemia Hematology Protein-Tyrosine Kinases medicine.disease respiratory tract diseases Leukemia Pyrimidines Imatinib mesylate Oncology Protein kinase domain Benzamides Imatinib Mesylate Cancer research Mutation testing Tyrosine kinase |
| Zdroj: | Leukemia Research. 33:1260-1265 |
| ISSN: | 0145-2126 |
| DOI: | 10.1016/j.leukres.2008.12.017 |
| Popis: | Sequential treatment with different tyrosine kinase inhibitors (TKIs) is one of the strategies for handling chronic myeloid leukemia (CML) in which dynamic change in Bcr-Abl kinase domain mutation is often an obstacle faced during TKI therapy. Here we report successful sequential therapy with different TKIs for the CML patient harboring V299L and E459K compound mutations. Molecular monitoring including quantitative analysis of BCR-ABL transcript level and mutation analysis were performed regularly for successful treatment. Additionally a drug-target complex was structurally modeled to investigate influence of amino acid substitutions on drug resistance, and to choose alternative TKI in sequential therapy, suggesting protein structural modeling can be useful approach in selecting alternative TKIs. |
| Databáze: | OpenAIRE |
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