Biological rationale and clinical use of interferon in the classical BCR-ABL-negative myeloproliferative neoplasms

Because of its antiapoptotic, antiproliferative, and immunomodulatory properties, interferon (IFN) has been broadly used as an antiviral and antineoplastic agent. These properties are particularly suitable for the treatment of the classical BCR-ABL-negative myeloproliferative neoplasms (MPN), including essential thrombocytosis (ET), polycythemia vera (PV), and myelofibrosis (MF). In the MPN, IFN has been shown to suppress megakaryopoiesis, inhibit erythroid colony-forming cells, suppress bone marrow fibroblast progenitors, induce cytogenetic remission, and reduce the JAK2 V617F allele burden, sometimes completely. Although efficacy has long been demonstrated in the MPN, toxicities were frequent with recombinant IFN, tempering enthusiasm. However, with pegylated-IFN, because of less toxicity, there has been renewed interest, and recent studies in the MPN have shown hematologic and molecular response or remission in ET and PV; a smaller study in early MF has shown IFN's potential to retard fibrosis. The role of IFN in the treatment of MPN is being re-evaluated on the basis of these studies, and will be better defined as results return from an ongoing international study.