Functional investigation of Stathmin 1 in proliferation, differentiation and apoptosis in acute promyelocytic leukemia model

• Grant number: 19/01700-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2019
• End date: April 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: João Agostinho Machado Neto
• Grantee: Hugo Passos Vicari
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Acute promyelocytic leukemia (APL) is associated with t (15; 17) (q22; q21) translocation, which results in the fusion of PML and RAR± genes, generating the hybrid gene PML-RAR±. The clinical course has been modified in recent years from acute rapidly fatal leukemia to one of the most curable AML subtypes. Although uncommon, resistance to target therapy may occur and the mechanisms involved are still unclear. Since molecular pathogenesis is well established in APL, this disease becomes an interesting model for the evaluation of cellular mechanisms of the participation of proliferation and differentiation-related oncoproteins, and the knowledge generated can be transposed into orphan haematological neoplasms of specific target therapy. In this sense, our research group has shown that the Stathmin 1 gene (STMN1), a cytoplasmic phosphoprotein that acts as a destabilizing microtubule that allows greater capacity for cell cycle progression and proliferation, is highly expressed in a cohort of 121 patients with APL. Preliminary functional studies indicate that microtubule dynamics is a potential target for APL cells, including ATRA-resistant cells. The present study aims to investigate the effects of Stathmin 1 inhibition on proliferation, cell cycle progression, apoptosis, cell differentiation, microtubule dynamics and in vivo tumorigenesis of human cell lines of sensitive LPA (NB4) or resistant to ATRA (NB4-R2). (AU)

Scientific publications

(4)

(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)

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)

VICARI, HUGO PASSOS; LIMA, KELI; COSTA-LOTUFO, LETICIA VERAS; MACHADO-NETO, JOAO AGOSTINHO. Cellular and Molecular Effects of Eribulin in Preclinical Models of Hematologic Neoplasms. CANCERS, v. 14, n. 24, p. 15-pg., 2022-12-01. (21/01460-1, 19/23864-7, 19/01700-2, 21/11606-3)

LIMA, KELI; VICARI, HUGO PASSOS; ELIAS GODOY CARLOS, JORGE ANTONIO; LIPRERI DA SILVA, JEAN CARLOS; DE FIGUEIREDO-PONTES, LORENA LOBO; REGO, EDUARDO MAGALHAES; MACHADO-NETO, JOAO AGOSTINHO. Obatoclax reduces cell viability of acute myeloid leukemia cell lines independently of their sensitivity to venetoclax. Hematology, Transfusion and Cell Therapy, v. 44, n. 1, p. 4-pg., 2022-02-26. (19/01700-2, 19/23864-7, 18/19372-9)

VICARI, HUGO PASSOS; LIMA, KELI; GOMES, RALPH DA COSTA; FERNANDES, DANIARA CRISTINA; LIPRERI DA SILVA, JEAN CARLOS; RODRIGUES JUNIOR, MANOEL TRINDADE; BARROSO DE OLIVEIRA, ALINE SILVA; DOS SANTOS, RICARDO NASCIMENTO; ANDRICOPULO, ADRIANO DEFINI; COELHO, FERNANDO; et al. Synthetic cyclopenta [b] indoles exhibit antineoplastic activity by targeting microtubule dynamics in acute myeloid leukemia cells. European Journal of Pharmacology, v. 894, MAR 5 2021. (19/01700-2, 13/07600-3, 19/23864-7, 15/17177-6, 17/24993-0)