Influence of cytarabine metabolic pathway polymorphisms in acute myeloid leukemia induction treatment

6533b7d5fe1ef96bd126524a

RESEARCH PRODUCT

Influence of cytarabine metabolic pathway polymorphisms in acute myeloid leukemia induction treatment

Salvador F. Aliño Virginia Bosó Juan Eduardo Megías-vericat Blanca Boluda José Cervera Rebeca Rodríguez-veiga Luis Rojas José Luis Poveda Luis Sendra María José Herrero Federico Moscardó Pau Montesinos David Martínez-cuadrón Miguel A. Sanz

subject

Male 0301 basic medicine Oncology Cancer Research Pharmacogenomic Variants efficacy Kaplan-Meier Estimate polymorphism 0302 clinical medicine Polymorphism (computer science)Genotype Remission Induction Cytarabine DCK Myeloid leukemia Hematology Middle Aged Prognosis Leukemia Myeloid Acute Oncology 030220 oncology & carcinogenesis Toxicity Female Metabolic Networks and Pathways medicine.drug Adult Antimetabolites Antineoplastic medicine.medical_specialty Adolescent Genotype acute myeloid leukemia Polymorphism Single Nucleotide Young Adult 03 medical and health sciences Internal medicine medicine Mucositis Humans Allele Alleles Aged Retrospective Studies Polymorphism Genetic business.industry medicine.disease Minor allele frequency 030104 developmental biology CDA Immunology Cytarabine business

description

Cytarabine is considered the most effective chemotherapeutic option in acute myeloid leukemia (AML). The impact of 10 polymorphisms in cytarabine metabolic pathway genes were evaluated in 225 adult de novo AML patients. Variant alleles of DCK rs2306744 and CDA rs602950 showed higher complete remission (p = .024, p = .045), with lower survival rates for variant alleles of CDA rs2072671 (p = .015, p = .045, p = .032), rs3215400 (p = .033) and wild-type genotype of rs602950 (p = .039, .014). Induction death (p = .033) and lower survival rates (p = .021, p = .047) were correlated to RRM1 rs9937 variant allele. In addition, variant alleles of CDA rs532545 and rs602950 were related to skin toxicity (p = .031, p = .049) and mucositis to DCK rs2306744 minor allele (p = .046). Other toxicities associated to variant alleles were hepatotoxicity to NT5C2 rs11598702 (p = .032), lung toxicity (p = .031) and thrombocytopenia to DCK rs4694362 (p = .046). This study supports the interest of cytarabine pathway polymorphisms regarding efficacy and toxicity of AML therapy in a coherent integrated manner.

year	journal	country	edition	language
2017-06-02

https://fundanet.iislafe.san.gva.es/publicaciones/ProdCientif/PublicacionFrw.aspx?id=7164