Assessment of signaling pathways in stem-cells of de novo acute myeloid leukemia

• Grant number: 11/17112-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2012
• End date: October 01, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Eduardo Magalhães Rego
• Grantee: Mariana Tereza de Lira Benício
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 14/23651-0 - Comparison of genome-wide DNA methylation mapping between CD34+CD38-ALDHhigh and CD34+CD38-ALDHint cell subsets isolated from acute myeloid leukemia patients, BE.EP.DR

Abstract

Acute Myeloid Leukemia (AML) comprises a heterogeneous group of disorders, whose pathophysiology relies on abnormalities in genes related to cell commitment, proliferation and apoptosis. The characterization of such abnormalities allowed the identification of prognostic markers, which in addition to guide the choice for risk-adapted therapy, also became targets for drug development. However, little progress has been made with regard to AML treatment other than acute promyelocytic leukemia associated to t(15;17). For two decades, AML patients have been uniformly treated with a combination of an anthracycline and cytarabine. Complete remission is often seen but it is frequently followed by relapse, attributed to the ineffectiveness of chemotherapy to eliminate leukemia stem-cells (LSC). How LSC are able to overcome chemotherapy damaging effects is not well known, but the activation of alternative signaling pathways would be a potential mechanism to explain the differences in LSC response to microenvironment stimuli. Therefore, this project has as its main goal the identification of aberrant signaling pathways in leukemia iniciating cells isolated from AML cell lineages, which are associated to a greater potential of engraftment after xenotransplantation, thus representing potential targets to therapeutic intervention.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE LIRA BENICIO, MARIANA TEREZA; TIBURCIO RIBEIRO, ANA FLAVIA; AMERICO, ANDRE D.; FURTADO, FELIPE M.; GLORIA, ANA B.; LIMA, ALEIDE S.; SANTOS, SILVANA M.; XAVIER, SANDRA G.; LUCENA-ARAUJO, ANTONIO R.; FAGUNDES, EVANDRO M.; et al. Evaluation of the European LeukemiaNet recommendations for predicting outcomes of patients with acute myeloid leukemia treated in low- and middle-income countries (LMIC): A Brazilian experience. Leukemia Research, v. 60, p. 109-114, SEP 2017. (08/57895-1, 11/17112-0)