JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2020

JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML

Tracy Dagher
Valérie Edmond

Résumé

Interferon α (IFNα) is used to treat JAK2 V617F-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 JAK2 V617F 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. .
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Dates et versions

hal-04055414 , version 1 (02-04-2023)

Identifiants

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Tracy Dagher, Nabih Maslah, Valérie Edmond, Bruno Cassinat, William Vainchenker, et al.. JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML. Journal of Experimental Medicine, 2020, 218, ⟨10.1084/jem.20201268⟩. ⟨hal-04055414⟩
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