Study of the association between gene expression of Rho subfamily of GTPases, TP53 and TP53 regulators in patients with acute myeloid leukemia

• Grant number: 23/11767-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Mariana Lazarini
• Grantee: Beatriz de Almeida Rodrigues
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy characterized by the abnormal proliferation of immature cells of myeloid origin (myeloblasts) in the bone marrow. Although knowledge of the disease has advanced in recent years, AML still has a variable prognosis and a high mortality rate, especially in the elderly. Mutations in TP53 are found in about 8% of de novo AML cases and are associated with low response rate to chemotherapy and poor prognosis. The two main p53 regulations involve MDM2-mediated degradation and the activation of p14ARF, which acts as a positive regulator by inhibiting MDM2. P53 signaling pathway is complex and new components have been described. Evidence indicates that the Rho GTPases RhoA, RhoB and RhoC participate in p53-mediated functions and pathways through different mechanisms.In this project, we will associate TP53, MDM2 and CDKN2A (p14ARF coding gene) gene expression with RhoA, RhoB and RhoC gene expression of in bone marrow samples of AML patients. Our results will contribute to the understanding of p53 signaling and its relation with Rho GTPases in AML.