JAK2V617F but not CALR mutations confer increased molecular responses to interferon-alpha via JAK1/STAT1 activation

Pegylated interferon-alpha (peg-IFNa) treatment induces molecular remissions (MR) in patients with myeloproliferative neoplasms (MPN), including partial MR (PMR) in 30-40% of patients. Here, we compared the efficacy of IFNa treatment in JAK2V617F vs. CALR-mutated cells and investigated the mechanisms of differential response. Retrospective analysis of MPN patients treated with peg-IFNa demonstrated that patients harboring the JAK2V617F mutation were more likely to achieve PMR than those with mutated CALR (p=0.004), while there was no significant difference in hematological response. In vitro experiments confirmed an upregulation of interferon-stimulated genes in JAK2V617F-positive 32D cells compared to their CALR-mutated counterparts, and higher IFNa doses were needed to achieve the same IFNa response in CALR- as in JAK2V617F mutant 32D cells. 4 Total samples were analyzed.