https://scholars.lib.ntu.edu.tw/handle/123456789/538766
標題: | Detection of BCR-ABL gene mutations in Philadelphia chromosome positive leukemia patients resistant to STI-571 cancer therapy | 作者: | Chien J.-H. JIH-LUH TANG Chen R.-L. Li C.-C. Lee C.P. |
關鍵字: | ALL; CML; dHPLC; Gene mutation; Imatinib; MRD; STI571 | 公開日期: | 2008 | 卷: | 32 | 期: | 11 | 起(迄)頁: | 1724-1734 | 來源出版物: | Leukemia Research | 摘要: | The ABL-BCR fusion protein is a constitutively activated tyrosine kinase thought to play a central role in chronic myeloid leukemia (CML) and Philadelphia (Ph) chromosome acute lymphoid leukemia (ALL). Targeting the tyrosine kinase activity of ABL-BCR has been shown to be a promising therapeutic strategy in treating this disorder. Among the tyrosine kinase inhibitors, STI571 is a very effective therapeutic agent when administered to CML patients in the stable chronic phase. However, it has been reported that many CML patients with blast cell crisis treated with STI571 relapsed and became resistant to STI571. In order to understand the possible molecular mechanisms underlying STI571 resistance caused by ABL gene mutations, we investigated 19 patients (18 CML patients and 1 Ph (+) ALL patient) who either relapsed after initial response or had no response to STI571 treatment. We used polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis, dHPLC, and direct DNA sequencing to analyze any possible mutations in exons 5 to 9 of the ABL gene. Our results showed that 5 out of 19 patients had various mutations between exons 5 and 7 of the ABL gene. The Ph (+) ALL patient had a Glu255Lys mutation in exon 5 and a Thr315Ile mutation in exon 7. The Glu255Lys substitution has a G to A change, and the Thr315Ile substitution has a C to T change in the ABL gene. The other unique mutations found in this study include: Tyr253His, Met351Thr, GAA tri-nucleotides insertion, and Leu213Pro. ? 2008 Elsevier Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-47249117433&doi=10.1016%2fj.leukres.2008.04.023&partnerID=40&md5=047fde9b3d1b6be018f937951129bc1a https://scholars.lib.ntu.edu.tw/handle/123456789/538766 |
ISSN: | 0145-2126 | DOI: | 10.1016/j.leukres.2008.04.023 | SDG/關鍵字: | BCR ABL protein; glutamine; histidine; imatinib; isoleucine; lysine; methionine; threonine; tyrosine; acute lymphoblastic leukemia; adult; amino acid substitution; article; cancer chemotherapy; cancer patient; chronic myeloid leukemia; clinical article; controlled study; DNA sequence; exon; female; gene mutation; high performance liquid chromatography; human; human cell; leukemia relapse; male; nucleotide sequence; Philadelphia chromosome positive cell; polymerase chain reaction; priority journal; restriction fragment length polymorphism; treatment response; Adult; Aged; Amino Acid Substitution; Antineoplastic Agents; Child; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Drug Resistance, Neoplasm; Female; Fusion Proteins, bcr-abl; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Mutation; Piperazines; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Prognosis; Protein-Tyrosine Kinases; Pyrimidines |
顯示於: | 醫學系 |
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