Impact of genetic ancestry on development, molecular characteristics and clinical outcome in adult patients with Acute Lymphoblastic Leukemia

• Grant number: 20/12842-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2021
• End date: February 29, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Magalhães Rego
• Grantee: Keli Cristina de Lima
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The etiology of Acute Lymphoblastic Leukemia (ALL) is not well established and complex interactions may be involved. Recently, the World Health Organization (WHO) has recognized the Philadelphia-like ALL (Ph-like) as a new provisional diagnostic entity that has a molecular signature similar to ALL Ph+ (BCR-ABL1 +) and is associated with an unfavorable prognosis. Some recurrent genetic alterations present in Ph-like ALL respond to specific therapeutic strategies and provide insights into personalized therapies, but due to the difficult definition of diagnosis, identifying and treating these patients is still a challenge. Recent evidence has shown higher incidence rates and unfavorable clinical outcomes in Latin ALL patients, especially a higher incidence of Ph-like ALL, suggesting components of genetic predisposition. As Brazil is a country founded from different continental origins, there is little knowledge of how admixture and/or ancestral genetic components impact the development and progression of ALL. Given the above, this research project aims to investigate the association of ethnic characteristics and developmental risk, molecular classification and clinical outcome in adult Brazilian ALL patients. As perceptive of this project, we have the implementation of the identification of Ph-like patients in a referral center, which has the potential to impact risk stratification and changes in the therapeutic conduct of ALL patients, as well as pioneering the study of genetic ancestry associations in adult ALL cohorts. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACHADO-NETO, JOAO AGOSTINHO; CARLOS, JORGE ANTONIO ELIAS GODOY; LIMA, KELI. miRNAs as prognostic predictors in acute myeloid leukemia. TRANSLATIONAL CANCER RESEARCH, v. N/A, p. 4-pg., 2023-06-25. (21/06138-0, 21/11606-3, 20/12842-0)

MACHADO-NETO, JOAO AGOSTINHO; DO NASCIMENTO, MARIANE CRISTINA; GARNIQUE, ANALI DEL MILAGRO BERNABE; LIMA, KELI. Data mining in acute myeloid leukemia: identification of disease biomarkers, prognostic factors, novel targets, and potential drugs. TRANSLATIONAL CANCER RESEARCH, v. N/A, p. 4-pg., 2023-08-15. (21/11606-3, 20/12842-0)

LIMA, KELI; PEREIRA-MARTINS, DIEGO ANTONIO; LINS DE MIRANDA, LIVIA BASSANI; COELHO-SILVA, JUAN LUIZ; LEANDRO, GIOVANA DA SILVA; WEINHAUSER, ISABEL; CAVAGLIERI, RITA DE CASSIA; LEAL, ALINE DE MEDEIROS; DA SILVA, WELLINGTON FERNANDES; ALENCAR DE LIMA LANGE, ANA PAULA; et al. The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy. BLOOD CANCER JOURNAL, v. 12, n. 11, p. 11-pg., 2022-11-09. (15/09228-0, 20/12842-0, 19/23864-7, 21/11606-3, 17/23117-1)

VICARI, HUGO PASSOS; COELHO-SILVA, JUAN LUIZ; PEREIRA-MARTINS, DIEGO A.; LUCENA-ARAUJO, ANTONIO ROBERTO; LIMA, KELI; LIPRERI DA SILVA, JEAN CARLOS; SCHEUCHER, PRISCILA SANTOS; KOURY, LUISA C.; DE MELO, RAUL A.; BITTENCOURT, ROSANE; et al. STMN1 is highly expressed and contributes to clonogenicity in acute promyelocytic leukemia cells. INVESTIGATIONAL NEW DRUGS, NOV 2021. (19/01700-2, 20/12842-0, 17/23117-1, 19/23864-7, 17/24993-0)

LIMA, KELI; DE MIRANDA, LIVIA BASSANI LINS; GARNIQUE, ANALI DEL MILAGRO BERNABE; DE ALMEIDA, BRUNA OLIVEIRA; DO NASCIMENTO, MARIANE CRISTINA; ALCANTARA, GUILHERME AUGUSTO SOUSA; MACHADO-SANTELLI, GLAUCIA MARIA; REGO, EDUARDO MAGALHAES; MACHADO-NETO, JOAO AGOSTINHO. The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells. CANCERS, v. 15, n. 15, p. 14-pg., 2023-08-01. (19/23864-7, 21/11606-3, 20/12842-0, 22/03316-8, 19/25421-5)