Analysis of FLT3 inhibitors action in interaction with conditioned medium from M1 Macrophages against FLT3+ acute myeloid leukemia

• Grant number: 24/02407-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: May 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Magalhães Rego
• Grantee: Lucca Marcon Losso
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Acute Myeloid Leukemia (AML) is a malignant disease that affects the myeloid progenitor cells of the bone marrow. It is a molecularly and clinically heterogeneous disease, what makes the prognostic variable and the treatment must cover this plurality of mutations. The most common treatment for AML is the conventional chemotherapy that objectives complete remission (CR). However, mutations in the FLT3 tyrosine kinase receptor leads to a worse prognosis and requires specific therapies. Among the new therapies, the use of inhibitors of the tyrosine kinase receptor, like the pharmaco midostaurin, have shown to be quite effective in improving the prognostic and rates of CR in patients. Even though these medications have been great allies in treatment, a significant part of patients still has recidive disease. In this context, deepening the studies around the tumoral microenvironment e the role of macrophages in the progression of AML can be a breakthrough in the search of new treatments.The macrophages can be separated in two groups, the M1 subtype, with pro-inflammatory and anti-tumoral functions, and the M2 subtype, with anti-inflammatory and pro-tumoral functions. The presence of M2 macrophages supports the development and progression of cancer, while M1 macrophages act in the eradication of tumoral cells due to their cytotoxic, phagocytic and defense cells recruitment properties, what makes this subtype of research interest. In this context, we pretend to cultivate FLT3+ leukemic cells in a conditioned media of M1 macrophages and treat them with different concentrations of midostaurin to further evaluate the anti-tumoral potential of this therapeutic strategy.