Germline genetic factors influence the outcome of interferon-α therapy in polycythemia vera

[Manouche]

« Interferon-α (IFN-α)–based therapies can induce sustained hematologic responses (HRs) and durable molecular responses (MRs) in polycythemia vera (PV) and other myeloproliferative neoplasms (MPNs). During treatment of PV, an HR reflects normalization of blood values, whereas a MR marks a substantial reduction of the malignant clone in the peripheral blood, when quantified by the allelic burden of the JAK2V617F mutation that drives the disease in 95% of patients with PV. IFN-α has been consistently reported to have a disease-modifying capacity whereby it selectively targets malignant cells, which induces durable MRs in some patients, whereas other patients respond insufficiently. Previous studies have suggested that certain features of disease-driving somatic mutations and genomic aberrations do not predict the response to treatment with IFN-α »

« Because deep MRs are indispensable for curative therapy, it is important to investigate whether increased treatment duration can overcome the dampening effect of functional IFNL4 on MR »

ashpublications.org/blood/a...

[hunter5582]

Interesting finding. Understanding the implications of both the somatic and germline mutations that impact MPNs and treatment if critical to moving the science forard. Glad to see more of this research emerging,