5 '-nucleotidase, cytosolic II genotype, and clinical outcome in patients with acute myeloid leukemia with intermediate-risk cytogenetics
Por:
Diaz-Santa, J, Rodriguez-Romanos, R, Coll, R, Osca, G, Pratcorona, M, Gonzalez-Bartulos, M, Garrido, A, Angona, A, Talarn, C, Tormo, M, Arnan, M, Vives, S, Salamero, O, Tuset, E, Lloveras, N, Diez, I, Zamora, L, Bargay, J, Sampol, A, Cruz, D, Vila, J, Sitges, M, Garcia, A, Vall-Llovera, F, Esteve, J, Sierra, J, Gallardo, D
Publicada:
1 dic 2022
Ahead of Print:
1 sep 2022
Resumen:
Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5 '-nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients younger than 50 years old with the NT5C2 rs10883841 AA genotype had lower overall survival (OS) (p: .003; HR 2.16, 95% CI 1.29-3.61) and lower disease-free survival (DFS) (p: .002; HR 2.45, 95% CI 1.41-4.27), associated to a higher relapse incidence (p: .010; HR 2.23, 95% CI 1.21-4.12). Interestingly, subgroup analysis showed that the negative effect of the NT5C2 rs10883841 AA genotype was detected in all subgroups except in patients with nucleophosmin mutation without high ratio FLT-3 internal tandem duplication. CDA polymorphisms were associated with the complete remission rate after induction chemotherapy, without influencing OS. Further studies are warranted to determine whether this pharmacogenomic approach may be helpful to individualize AML treatment.
Filiaciones:
Diaz-Santa, J:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Rodriguez-Romanos, R:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Coll, R:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Osca, G:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Pratcorona, M:
Univ Autonoma Barcelona, Hematol Dept, Hosp Santa Creu & St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Barcelona, Spain
Gonzalez-Bartulos, M:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Garrido, A:
Univ Autonoma Barcelona, Hematol Dept, Hosp Santa Creu & St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Barcelona, Spain
Angona, A:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Talarn, C:
Hosp Joan 23, Hematol Dept, Inst Catala Oncol, Tarragona, Spain
Tormo, M:
Hosp Clin Univ, Hematol Dept, Valencia, Spain
Arnan, M:
Univ Barcelona, Inst Catala Oncol, Hematol Dept, Hosp Duran I Reynals, Barcelona, Spain
Univ Barcelona, Inst Invest Biomed Bellvitge IDIBELL, Barcelona, Spain
Vives, S:
Univ Autonoma Barcelona, Inst Catala Oncol, Hosp Germans Trias & Pujol, Barcelona, Spain
Univ Autonoma Barcelona, Josep Carreras Res Inst, Barcelona, Spain
Salamero, O:
Hosp Univ Vall dHebro, Hematol Dept, Barcelona, Spain
Tuset, E:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Lloveras, N:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Diez, I:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Zamora, L:
Univ Autonoma Barcelona, Inst Catala Oncol, Hosp Germans Trias & Pujol, Barcelona, Spain
Univ Autonoma Barcelona, Josep Carreras Res Inst, Barcelona, Spain
Bargay, J:
Hosp Son Llatzer, Hematol Dept, Palma De Mallorca, Spain
Sampol, A:
Hosp Son Espases, Hematol Dept, Palma De Mallorca, Spain
Cruz, D:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Vila, J:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Sitges, M:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
Garcia, A:
Hosp Arnau Vilanova, Hematol Dept, Lleida, Spain
Vall-Llovera, F:
Hosp Mutua Terrassa, Hematol Dept, Terrassa, Spain
Esteve, J:
Univ Barcelona, Hosp Clin Barcelona, Hematol Dept, IDIBAPS, Barcelona, Spain
Sierra, J:
Univ Autonoma Barcelona, Hematol Dept, Hosp Santa Creu & St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Barcelona, Spain
Gallardo, D:
Univ Girona, Inst Catala Oncol, Hematol Dept, Hosp Dr Josep Trueta, Girona, Spain
Univ Girona, Inst Invest Biomed Girona IDIBGI, Girona, Spain
Univ Girona, Josep Carreras Res Inst, Girona, Spain
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