Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene

Autor: Juan Collazo-Jaloma, Etta Rozen-Fuller, Adolfo Martínez-Tovar, Rafael Cerón-Maldonado, Irma Olarte-Carrillo, Juan Julio Kassack-Ipiña, Guillermo Meléndez-Mier, Christian Omar Ramos-Peñafiel
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Male
medicine.medical_treatment
lcsh:Medicine
Drug resistance
Kaplan-Meier Estimate
0302 clinical medicine
Leukocytes
Odds Ratio
Medicine
Prospective Studies
media_common
education.field_of_study
Remission Induction
General Medicine
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
ATP binding cassette subfamily B member 1 (ABCB1)
Metformin
Treatment Outcome
030220 oncology & carcinogenesis
Female
medicine.drug
Drug
Adult
medicine.medical_specialty
ATP Binding Cassette Transporter
Subfamily B
Adolescent
media_common.quotation_subject
Population
Acute lymphoblastic leukemia (ALL)
General Biochemistry
Genetics and Molecular Biology
Immunophenotyping
03 medical and health sciences
Young Adult
Internal medicine
Humans
education
Survival analysis
Chemotherapy
business.industry
Research
Gene Expression Profiling
lcsh:R
Odds ratio
Confidence interval
030104 developmental biology
Quantitative real-time polymerase chain reaction (qRT-PCR)
Drug Resistance
Neoplasm
Neoplasm Recurrence
Local
business
Zdroj: Journal of Translational Medicine
Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-9 (2018)
ISSN: 1479-5876
Popis: Background In acute lymphoblastic leukemia (ALL), high ABCB1 gene expression has been associated with treatment resistance, which affects patient prognosis. Many preclinical reports and retrospective population studies have shown an anti-cancer effect of metformin. Therefore, the objective of this study was to assess the effect of metformin on the treatment regimen in patients with ALL who exhibited high levels of ABCB1 gene expression and to determine its impact on overall survival. Methods A total of 102 patients with ALL were recruited; one group (n = 26) received metformin, and the other received chemotherapy (n = 76). Measurement of ABCB1 transcript expression was performed using qRT-PCR prior to treatment initiation. Survival analysis was performed using Kaplan–Meier curves. The impact of both the type of treatment and the level of expression on the response (remission or relapse) was analyzed by calculating the odds ratio. Results The survival of patients with high ABCB1 expression was lower than those with low or absent ABCB1 gene expression (p = 0.030). In the individual analysis, we identified a benefit to adding metformin in the group of patients with high ABCB1 gene expression (p = 0.025). In the metformin user group, the drug acted as a protective factor against both therapeutic failure (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.0037–1.53) and early relapse (OR 0.05, 95% CI 0.0028–1.153). Conclusion The combined use of metformin with chemotherapy is effective in patients with elevated levels of ABCB1 gene expression. Trial registration NCT 03118128: NCT
Databáze: OpenAIRE
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