RIPK1 inhibition enhances the therapeutic efficacy of chidamide in FLT3-ITD positive AML, both in vitro and in vivo.
Leuk Lymphoma
; 63(5): 1167-1179, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-34865571
ABSTRACT
Acute myeloid leukemia (AML) with FLT3-ITD mutation accounts for a large proportion of relapsed/refractory AML with poor prognosis. RIPK1 is a known key regulator of necroptosis and RIPK1 inhibition shows anti-AML effects in vitro. Chidamide is a histone deacetylase inhibitor (HDACi) with proven ability to induce apoptosis in FLT3-ITD positive AML cells. In the present study, we evaluated the effects of the combination of 22b, a novel RIPK1 inhibitor, and chidamide on proliferation and apoptosis in FLT3-ITD positive AML cell lines and primary cells. The results showed that 22b could significantly enhance the anti-leukemia effect of low-dose chidamide both on cell lines and primary cells. In a subcutaneous xenograft AML model, the combination of 22b and chidamide exhibited obviously elevated anti-tumor activity. In conclusion, our results support that the combination of RIPK1 inhibitor 22b and chidamide may be a novel therapeutic avenue for FLT3-ITD positive AML patients.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
Límite:
Humans
Idioma:
En
Revista:
Leuk Lymphoma
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2022
Tipo del documento:
Article
País de afiliación:
China