GENETIC POLYMORPHISMS OF XENOBIOTIC METABOLISM ENZYMES
IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
Mia Ratwita Andarsini
Child Health Departement Medical Faculty Airlangga UniversityDr Soetomo Hospital
Acute Lymphoblastic Leukemia (ALL) is the commonest malignancy in children. In 2017, there was 143 new cases of childhood ALL in Dr Soetomo Hospital Surabaya. Although the efficacy of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) patients has significantly increased in the last 20 years, but still 25% of them has failed to remission. Many factors influence pharmacokinetics and pharmacodynamics of antileukemic agents, such as genetic polymorphisms of xenobiotic metabolism enzymes which ispolymorphisms in genes that encode for the proteins involved in the metabolisms of antileukemic agents. This genetic polymorphisms can caused alterations of the activity or function of drug-metabolizing enzymes and transportersand then can influenced the efficacy or toxicity (or both) of antileukemic agents.
For example, a patient with genetic polymorphisms of MTHFR C677T has four time increased possibility of methotrexate resistance and a patient with genetic polimorphisms of TS 5’-UTR 3R/3R six time increased possibility of methotrexate resistance. Therefore giving the same dosages of methotrexate, can reduced accumulation of activemetabolites in leukemia cells, due to decrease of metabolizing enzymes and then can associated with a poor outcome in ALL. Until now pharmacogenetic studies havefocused on single gene candidates, based onthe pharmacokineticsand pharmacodynamics characteristics of a specificdrug.It still need further investigation to to identifythe entire set of genes that are relevant to thepharmacological effects of antileukemic drugs.
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