CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia.
Cancer Res
; 83(17): 2824-2838, 2023 09 01.
Article
em En
| MEDLINE
| ID: mdl-37327406
ABSTRACT
Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival. CD36 was dispensable for lipid uptake but fostered blast migration through its binding with thrombospondin-1. CD36-expressing blasts, which were largely enriched after chemotherapy, exhibited a senescent-like phenotype while maintaining their migratory ability. In xenograft mouse models, CD36 inhibition reduced metastasis of blasts and prolonged survival of chemotherapy-treated mice. These results pave the way for the development of CD36 as an independent marker of poor prognosis in AML patients and a promising actionable target to improve the outcome of patients. SIGNIFICANCE:
CD36 promotes blast migration and extramedullary disease in acute myeloid leukemia and represents a critical target that can be exploited for clinical prognosis and patient treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França