Functional and molecular investigation of the correlation between autophagy, NLRP3-inflammasome and hemostasis on acute myeloid leukemia

• Grant number: 22/03871-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2023
• End date: September 30, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fabíola Traina
• Grantee: Brunno Gilberto Santos de Macedo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Acute myeloid leukemia (AML) comprehends a heterogeneous and complex group of hematological neoplasms characterized by the affection of hematopoietic stem and progenitor cells by (epi)genetic insults that trigger these cells clonal expansion, hypofunctional cells accumulation and bone marrow remodeling that leads to impairment of normal hematopoiesis.AML's biology has been extensively studied in order to prospect new therapeutic approaches.The main point of the present project is to evaluate how autophagy, NLRP3-inflammasome, and hemostasis, three functionally abnormal biological processes on AML, are transcricional and functionally correlated for sustainment of a leukemia-promoting state. The correlation among gene expression of autophagy, inflammasome, and hemostasis genes (247 genes) shall be initially established from a couple of independent public AML cohorts transcriptomic data analyses: The Cancer Genome Atlas (TCGA, 2013) cohort and Oregon Health and Science University AML cohort (BeatAML, 2018) through R (version 4.2.1) programming environment and language. In silico identification of groups of genes which gene expression are mutually correlated among the three biological processes shall drive further investigation to be set on leukemia cell lines (THP-1 and OCI-AML3) in order to comprehend the functional consequences, as cell proliferation, death and viability rates, as well as autophagy and inflammasome modulation, of sole and associated inhibition of these processes. The investigation of less explored but reportedly abnormal mechanisms on AML context can represent a relevant biological ground to potentially transpose into disease classification and therapeutic management.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MACEDO, Brunno Gilberto Santos de. Molecular and functional interaction between autophagy and inflammasome in acute myeloid leukemia. 2024. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.