Paving the way to improve therapy for Myeloproliferative Neoplasms

Abstract

Long-acting IFNα induces durable molecular responses in myeloproliferative neoplasms. Emerging studies, including Saleiro et al. recently published in Nature Communications , have identified promising candidates that may synergise with IFNα by targeting stem cell function or feedback loops that mediate treatment resistance.

Interferon and myeloproliferative neoplasms: Evolving therapeutic approaches

“…MPNs represent a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders that lead to expansion of the myeloid compartment. [ 10 ] This group includes chronic myeloid leukemia (CML), which is driven by the BCR/ABL fusion protein generated from the characteristic Philadelphia chromosome as a result of chromosomal rearrangement t(9;22)(q34;q11). [ 11 ] IFNα induces major responses in CML and was long a mainstay of treatment, but it has since been overtaken by tyrosine kinase inhibitors (TKIs) directly targeting the fusion protein.…”

“…[ 2 ] Nevertheless, it remains a viable therapeutic option in BCR/ABL negative MPNs, especially in polycythemia vera (PV) and essential thrombocytosis (ET). [ 10 ] These MPNs are remarkable for the ubiquitous presence of mutations in Janus kinase 2 (JAK2), calreticulin (CALR), or MPL (thrombopoietin receptor) genes that lead to constitutive activation of the JAK‐STAT pathway. [ 12 ] The accumulation of additional mutations appears to affect the clonal propensity of the disease and whether fibrotic or leukemic transformation is likely.…”

Myeloproliferative Neoplasms: Contemporary Review and Molecular Landscape

“…They have long been known to have activity against MPN. However, poor pharmacokinetics and the adverse effect profile of earlier forms limit their usage [95]. Progressive modification of the recombinant product has prompted renewed interest in recent years, with several regulatory approvals and other products in the pipeline.…”