Study of gene and protein expression in patients with Chronic Myeloid Leukemia

• Grant number: 13/05397-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2013
• End date: November 30, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Anderson Ferreira da Cunha
• Grantee: Lara Woldmar
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by a reciprocal chromosomal translocation between the long arms of chromosomes 9 and 22, which originates a short chromosome 22 known as the Philadelphia (Ph) chromosome. In this translocation t(9;22)(q34;q11), the union between two genes occurs, generating a leukemia-specific gene, the BCR-ABL; the chimeric protein formed by the BCR-ABL fusion has elevated tyrosine kinase activity, which is responsible for the pathogenicity of the disease. This activity results in the phosphorylation of various substrates, leading to the activation of signal transduction cascades, which affects cellular growth and cellular differentiation. Peroxiredoxins (Prdx) are a family of multifunctional antioxidant thioredoxin-dependent peroxidases that not only protect cells against oxidative stress but also modulate signaling cascades that apply hydrogen peroxide as a second messenger molecule and regulate cell proliferation. The Prdx are therefore related to tumorigenesis while acting as cellular antioxidants, regulating cell apoptosis and proliferation, modulating signaling cascades and interacting with oncogene products and molecules related to tumorigenesis. However, the relation between the Prdx and the CML has not yet been studied; therefore, this project aims to evaluate the genetic expression and activity of Prdx in patients with CML, in order to establish relations between the disease and the Prdx and to contribute to the knowledge of the disease, improving the understanding of its mechanisms and helping to elaborate new treatments.