Role of the TXNRD3 gene in methotrexate resistance in pediatric acute lymphoid leukemia

• Grant number: 23/03402-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: José Andrés Yunes
• Grantee: Rudolph Rezende Vera
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Acute lymphoblastic leukemia (ALL) represents the most common type of cancer in childhood, accounting for a quarter of all childhood malignancies. Although approximately 80% of patients are cured, the main cause of treatment failure is resistance to drugs used during treatment. Methotrexate (MTX) is one of the main drugs used to combat ALL, as it inhibits nucleotide synthesis and induces apoptosis of leukemic blasts. However, despite its high efficacy, some patients are resistant to MTX treatment, leading to disease relapse and notably decreasing the chance of a cure. Previous studies have linked this resistance to MTX to glutathione (GSH) levels, and furthermore, it has been established through gene expression analysis that eight genes are correlated with GSH concentration. The aim of the present study is to elucidate the role of one of the genes related to GSH concentration, the TXNRD3 gene, in MTX resistance.