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Profiling gene mutations, translocations, and multidrug resistance in pediatric acute lymphoblastic leukemia: a step forward to personalizing medicine.
Medical Oncology 2016 September
Precise risk stratification and tailored therapy in acute lymphoblastic leukemia (ALL) can lead to enhanced survival rates among children. Translocations and mutations along with multidrug resistance markers are important factors that determine therapeutic efficacy. Gene mutation profiling of patients at the time of diagnosis can offer accurate clinical decision-making. Multiplex PCR was used to screen for various translocations, mutations, and P-glycoprotein (P-gp) status in pediatric ALL samples. The roles of P-gp were analyzed at the transcriptional and translational levels by using real-time PCR and immunoblotting, respectively. ALL specific cell line Jurkat was used to validate the functional role of P-gp in imparting drug resistance by siRNA knockdown studies. Co-occurrence of translocations and mutations contributes to cellular drug resistance. Presence of any translocation in addition to FLT3/ITD hints for overactive P-gp. Co-occurrence of E2A/PBX and TEL/AML has also been positively correlated with P-gp status. Multiplex PCR provides a rapid and cost effective technique for profiling translocations, mutations, and multidrug resistance status that determines what therapy patients could be administered. Mutation profiling in patients for analyzing genetic lesions along with drug resistance profiling will help improve risk stratification and personalized medicine, thereby increasing the treatment success rates among pediatric patients with leukemia.
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