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  • Title: Influence of polymorphisms in anthracyclines metabolism genes in the standard induction chemotherapy of acute myeloid leukemia.
    Author: Megías-Vericat JE, Martínez-Cuadrón D, Herrero MJ, Rodríguez-Veiga R, Solana-Altabella A, Boluda B, Ballesta-López O, Cano I, Acuña-Cruz E, Cervera J, Poveda JL, Sanz MÁ, Aliño SF, Montesinos P.
    Journal: Pharmacogenet Genomics; 2021 Aug 01; 31(6):133-139. PubMed ID: 33675324.
    Abstract:
    OBJECTIVES: Genetic variability in anthracycline metabolism could modify the response and safety of acute myeloid leukemia (AML) induction. METHODS: Polymorphisms in genes that encodes enzymes of anthracyclines metabolic pathway (CBR3: rs1056892, rs8133052, NQO1: rs1800566, NQO2: rs1143684, NOS3: rs1799983, rs2070744) were evaluated in 225 adult de novo AML patients. RESULTS: The variant CBR3 rs8133052 was associated with lower hepatotoxicity (P = 0.028). Wild-type genotype of NQO2 rs1143684 was related to higher complete remission (P = 0.014), and the variant allele with greater gastrointestinal toxicity (P = 0.024). However, the variant genotype of NQO1 rs1800566 was associated with mucositis (P = 0.018), but heterozygous genotype showed less gastrointestinal toxicity (P = 0.028) and thrombocytopenia (P = 0.009). Protective effects against nephrotoxicity and thrombocytopenia were reported with variant NOS3 rs1799983 (P = 0.006, P = 0.014), whereas carriers of NOS3 rs2070744 showed higher hepatotoxicity and thrombocytopenia (P = 0.017, P = 0.013). CONCLUSIONS: This study supports the influence of genetic variability of idarubicin metabolizing could be critical in predicting anthracycline-induced toxicities.
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