An updated outlook on autophagy mechanism and how it supports acute myeloid leukemia maintenance

Autor(es)

de Macedo, Brunno Gilberto Santos ; de Melo, Manuela Albuquerque ; Pereira-Martins, Diego Antonio ; Machado-Neto, Joao Agostinho ; Traina, Fabiola

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER; v. 1879, n. 6, p. 11-pg., 2024-11-01.

Resumo

The gradual acquisition of genetic and epigenetic disturbances bestows malignant traits upon hematopoietic stem cells, subverting them into a founder and reservoir cell for de novo acute myeloid leukemia (AML) known as leukemic stem cells (LSC). Beyond its molecular heterogeneity, AML is also characterized by rewiring biological processes to support its onset and maintenance. LSC were observed to inherently and actively trigger mitochondrial turnover through selective autophagic removal such that impairing the process led to cell differentiation at the expense of its stemness. This review provides a current take on autophagy regulation mechanisms according to the current molecular characterization of the process; describes autophagy as a drug resistance mechanism, and a pivotal mechanism whereby LSC harmonize their strong reliance on mitochondrial respiration to obtain energy, and their necessity for lower internal oxidative stress to avoid exhaustion. Therefore, targeting autophagy presents a promising strategy to promote long-term remissions in AML. (AU)

• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 21/11112-0 - Avaliação da autofagia como mecanismo limitante da eficiência terapêutica de inibidores farmacológicos de FLT3 em leucemia mieloide aguda
• Beneficiário: Manuela Albuquerque de Melo
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 22/03871-1 - Investigação molecular e funcional da correlação entre autofagia, inflamassoma NLRP3 e hemostasia na leucemia mieloide aguda
• Beneficiário: Brunno Gilberto Santos de Macedo
• Modalidade de apoio: Bolsas no Brasil - Mestrado