JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML.
J Exp Med
; 218(2)2021 02 01.
Article
em En
| MEDLINE
| ID: mdl-33075130
ABSTRACT
Interferon α (IFNα) is used to treat JAK2V617F-driven myeloproliferative neoplasms (MPNs) but rarely clears the disease. We investigated the IFNα mechanism of action focusing on PML, an interferon target and key senescence gene whose targeting by arsenic trioxide (ATO) drives eradication of acute promyelocytic leukemia. ATO sharply potentiated IFNα-induced growth suppression of JAK2V617F patient or mouse hematopoietic progenitors, which required PML and was associated with features of senescence. In a mouse MPN model, combining ATO with IFNα enhanced and accelerated responses, eradicating MPN in most mice by targeting disease-initiating cells. These results predict potent clinical efficacy of the IFNα+ATO combination in patients and identify PML as a major effector of therapy, even in malignancies with an intact PML gene.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon-alfa
/
Janus Quinase 2
/
Proteína da Leucemia Promielocítica
/
Trióxido de Arsênio
/
Transtornos Mieloproliferativos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article