| Texto completo | |
| Autor(es): |
Machado-Neto, Joao Agostinho
;
Vicari, Hugo Passos
;
da Silva, Jean Carlos Lipreri
;
Lima, Keli
Número total de Autores: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOCHEMICAL SOCIETY TRANSACTIONS; v. N/A, p. 10-pg., 2025-09-22. |
| Resumo | |
Acute leukemias are hematological malignancies characterized by the uncontrolled proliferation of immature bone marrow cells, disrupting normal hematopoiesis. These diseases, classified into acute lymphoblastic leukemia and acute myeloid leukemia (AML), often result from acquired genetic alterations that drive deregulated cell growth and inhibit differentiation. The cytoskeleton has emerged as a promising therapeu- tic target due to its pivotal role in cellular processes such as adhesion, motility, and division. Among its components, stathmin 1 (STMN1) and ezrin (EZR) stand out for their significant involvement in the pathogenesis and progression of acute leukemias. STMN1, a regulator of microtubule dynamics, is associated with chromosomal instability and leukemic cell proliferation, and is frequently overexpressed in these malignancies. Anti-microtubule agents, such as paclitaxel, eribulin, and cyclopenta[b]indole derivatives have demonstrated the ability to inhibit STMN1 by inducing its phosphorylation at regulatory sites, thereby impairing cell viability and promoting apoptosis. EZR, a membrane-actin linker protein, plays a critical role in cell signaling and tumor survival. Its overexpression has been correlated with poor prognosis in AML. Pharmacological inhibitors like NSC305787 have shown efficacy in reducing cell viability, modulating key pathways such as PI3K (phosphatidylinositol-3-kinase)/AKT (AKT serine-threonine protein)/mTOR (mamma- lian target of rapamycin), and enhancing the activity of standard chemotherapeutics, thereby supporting their potential use in combination therapies. This review aims to explore the roles of STMN1 and EZR in the pathogenesis of acute leukemias, assessing their potential as therapeutic targets. The goal is to synthesize recent evidence to guide the development of more effective inhibitors, focusing on overcoming therapeutic resistance and tailoring treatments to individual profiles. (AU) | |
| Processo FAPESP: | 19/23864-7 - Análise compreensiva de dados genômicos para identificação e validação de novos alvos terapêuticos envolvidos na regulação de citoesqueleto celular em Leucemias agudas |
| Beneficiário: | João Agostinho Machado Neto |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/11606-3 - Investigação dos efeitos antineoplásicos de novos inibidores de PIP4K2 e HDAC em neoplasias hematológicas |
| Beneficiário: | João Agostinho Machado Neto |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |