Novel strategies for AML treatment: developing new technologies targeting the bone marrow niche

• Grant number: 22/14101-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: March 01, 2023
• End date: August 31, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Maura Lima Pereira Bueno
• Supervisor: Sandra Pinho
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Illinois at Chicago (UIC), United States
• Associated to the scholarship: 21/05230-0 - Activity of WNT signaling pathway inhibitors in in vitro models, BP.DD

Abstract

Acute Myeloid Leukemia (AML) corresponds to a hematological neoplasm that includes the abnormal and disordered proliferation of immature blood and bone marrow (BM) cells quite common in people over 65 years of age. BM transplantation is considered the only curative treatment for AML; however, it is not applicable to most patients due to age and the presence of comorbidities. In addition, chemotherapeutic agents currently administered in clinical practice result in high morbidity and limited efficiency due to poor differentiation capacity between healthy and neoplastic cells, causing adverse effects. Treatment-related toxicity and prolonged hospitalization, often necessary, have a profound impact on the quality of life of these patients. Thus, there is a need for novel and more efficient therapeutic strategies with fewer side effects and with selective action on neoplastic cells, without altering normal cells. In this context, compounds whose actions are based on the modulation of deregulated pathways in AML or on the interaction between hematopoietic cells and their niche correspond to possible candidates for the development of new therapeutic strategies. We propose to develop new strategies for antitumor therapy based on novel non commercialized compounds, such as inhibitors of MCL-1, BCL-2, Src kinase, ERK, and MEK proteins, as well as the improvement of crucial methods for the assessment of drug effects, such as in vivo analyses using the MLL-AF9 mouse AML model, and ex vivo investigation of the tumor microenvironment by a 3D co-culture system. (AU)