Rellevance of ERK/MAPK pathway in the resistance of AML to NK cell therapy

• Grant number: 18/15622-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2018
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: WELBERT DE OLIVEIRA PEREIRA
• Grantee: Gabriel Herculano Lopes
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Acute myeloid leukemia (AML) is a hematological cancer characterized by increased proliferation of abnormal and precursor cells of the leukocyte myeloid line, called blasts. In addition to being non-functioning cells, they accumulate in the bone marrow, interfering in the normal hematopoiesis. The chemotherapeutic treatment for leukemia is still not very effective. Although it can cure part of the patients, for most of them the prognosis is poor, especially when it comes to relapsing disease. Within this context, immunotherapy appears as a promising therapeutic approach in this decade, especially NK cell based immunotherapy. NK cell's biological functions in immunovigilance against cancer have already been widely described in the literature. However, considering that cancer is a complex and multifactorial disease, several mutations and anomalous changes of signaling pathways in leukemic cells have been reported. Potentially even the immunotherapeutic approaches with the use of NK cells may need the use of concomitant treatment that acts in a synergistic or additive way. That scenario justifies the importance of the investigation of the ERK/MAPK signaling pathway, considering that this is an important leukemic cell signaling pathway and it is related to proliferation and resistance to apoptosis. The objective of this project is to evaluate the activation status of ERK/MAPK pathway in AML and investigate the effect of pharmacological inhibition of this signaling on NK cell-induced apoptosis resistance.