Overexpression of dihydrofolate reductase is a factor of poor survival in acute lymphoblastic leukemia

Organista‑Nava,Jorge; Gómez‑Gómez,Yazmín; Illades‑Aguiar,Berenice; Rivera‑Ramírez,Ana   Bertha; Saavedra‑Herrera,Mónica   Virginia; Leyva‑Vázquez,Marco   Antonio

doi:10.3892/ol.2018.8429

Overexpression of dihydrofolate reductase is a factor of poor survival in acute lymphoblastic leukemia

Authors:
- Jorge Organista‑Nava
- Yazmín Gómez‑Gómez
- Berenice Illades‑Aguiar
- Ana Bertha Rivera‑Ramírez
- Mónica Virginia Saavedra‑Herrera
- Marco Antonio Leyva‑Vázquez
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Affiliations: Laboratory of Molecular Biomedicine, School of Chemical‑Biological Sciences, Guerrero State University, Chilpancingo, Guerrero 39090, Mexico, Research Department, State Cancer Institute, Arturo Beltran Ortega, Acapulco, Guerrero 39570, Mexico
Published online on: April 4, 2018 https://doi.org/10.3892/ol.2018.8429
Pages: 8405-8411
Copyright: © Organista‑Nava et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Abstract. Dihydrofolate reductase (DHFR) has an important function in DNA synthesis and is a target of methotrexate, which is a crucial treatment option for acute lymphoblastic leukemia (ALL). However, the number of studies conducted to date on DHFR expression in childhood ALL is limited. The aim of the present study was to determine whether the expression of DHFR is associated with survival in childhood ALL. The expression of DHFR in 96 children with ALL and 100 control individuals was determined using reverse transcription‑quantitative polymerase chain reaction. The results of the present study demonstrated that the expression of DHFR mRNA in children with ALL was significantly increased (P<0.001), compared with that in the control group. In addition, increased levels of DHFR mRNA were observed in patients with B‑cell lineage, compared with patients with T‑cell lineage ALL (P<0.05). The Kaplan‑Meier estimator analysis revealed that children with ALL who exhibited increased levels of DHFR mRNA had a decreased overall survival time (P<0.05). It was observed that certain patient prognostic features (including age, sex, white blood cell count and high DHFR expression), are associated with poor survival (log‑rank test, P<0.05). Therefore, the results of the present study indicated that DHFR upregulation is a factor for poor survival in ALL.

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