| First Author | Dagher T | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 2 | PubMed ID | 33075130 |
| Mgi Jnum | J:307781 | Mgi Id | MGI:6509797 |
| Doi | 10.1084/jem.20201268 | Citation | Dagher T, et al. (2021) JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML. J Exp Med 218(2) |
| abstractText | Interferon alpha (IFNalpha) is used to treat JAK2V617F-driven myeloproliferative neoplasms (MPNs) but rarely clears the disease. We investigated the IFNalpha 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 IFNalpha-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 IFNalpha enhanced and accelerated responses, eradicating MPN in most mice by targeting disease-initiating cells. These results predict potent clinical efficacy of the IFNalpha+ATO combination in patients and identify PML as a major effector of therapy, even in malignancies with an intact PML gene. |
