OBJECTIVES： Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib （IM） has caused significant changes in treatment course and has increased the survival of patients. A small group of patient...OBJECTIVES： Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib （IM） has caused significant changes in treatment course and has increased the survival of patients. A small group of patients show resistance to IM. Acquired mutations in tyrosine kinase domain of BCR-ABL protein are a mechanism for development of resistance. T315I is one of the most common acquired mutations in this domain, which occurs in ATP binding site and inhibits the formation of hydrogen bond with IM. The aim of this study was to evaluate the prevalence of this mutation in BCR/ABL-positive CML and ALL patients. METHODS： To conduct this study, 60 BCR-ABL-positive patients （including 50 CML and 10 ALL patients） who were subject to treatment with IM were selected. After taking the samples, presence of T315I mutation was assessed using ARMS- PCR on cDNA and its polymorphism was evaluated by sequencing. RESULTS： The results showed that among 60 patients, only three patients had T315I mutation, which was detected using ARMS technique. The three patients bearing mutation were afflicted with CML and no significant association was found between blood parameters with duration of treatment in presence of mutation. CONCLUSIONS： The mutation was found in three CML patients, which indicated lower likelihood and diagnostic value of this mutation in ALL patients. Given the negative direct sequencing results in T3151 patients, it can be concluded that ARMS- PCR is a more sensitive technique when the number of cancer cells is low in patients during treatment.展开更多
文摘OBJECTIVES： Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib （IM） has caused significant changes in treatment course and has increased the survival of patients. A small group of patients show resistance to IM. Acquired mutations in tyrosine kinase domain of BCR-ABL protein are a mechanism for development of resistance. T315I is one of the most common acquired mutations in this domain, which occurs in ATP binding site and inhibits the formation of hydrogen bond with IM. The aim of this study was to evaluate the prevalence of this mutation in BCR/ABL-positive CML and ALL patients. METHODS： To conduct this study, 60 BCR-ABL-positive patients （including 50 CML and 10 ALL patients） who were subject to treatment with IM were selected. After taking the samples, presence of T315I mutation was assessed using ARMS- PCR on cDNA and its polymorphism was evaluated by sequencing. RESULTS： The results showed that among 60 patients, only three patients had T315I mutation, which was detected using ARMS technique. The three patients bearing mutation were afflicted with CML and no significant association was found between blood parameters with duration of treatment in presence of mutation. CONCLUSIONS： The mutation was found in three CML patients, which indicated lower likelihood and diagnostic value of this mutation in ALL patients. Given the negative direct sequencing results in T3151 patients, it can be concluded that ARMS- PCR is a more sensitive technique when the number of cancer cells is low in patients during treatment.
