The Intricate Dance Between Inflammation and Myeloproliferative Neoplasms: From Origins to Outcomes

TL;DR

This paper reviews how inflammation contributes to myeloproliferative neoplasms and how therapies targeting inflammation can improve outcomes.

Contribution

The paper reframes MPNs as a disorder of immune and stromal interactions, emphasizing inflammation as both a driver and a therapeutic target.

Findings

Chronic inflammatory stress promotes the expansion of MPN-associated clones like JAK2.

Inflammatory cytokines sustain myeloproliferation and contribute to bone marrow fibrosis.

JAK inhibitors and newer agents reduce inflammation, offering therapeutic benefits.

Abstract

Myeloproliferative neoplasms (MPNs) lie at the intersection of malignancy and chronic inflammatory disease. This review summarizes current understanding of how inflammation drives MPN pathogenesis, from clonal initiation to progression and symptom burden, and explores how emerging therapies modulate the inflammatory microenvironment.

Evidence from human genetics, epidemiology, and experimental models shows that chronic inflammatory stress promotes the expansion of JAK2- and other MPN-associated clones. Inflammatory cytokine networks sustain myeloproliferation, reshape the bone marrow niche, and contribute to fibrosis. JAK inhibitors remain the cornerstone of therapy and exert much of their clinical benefit through suppression of cytokine signaling. Newer agents also mitigate inflammation through complementary mechanisms.

Inflammation is inseparable from MPN biology and represents both a driver and a therapeutic target. Reframing MPN as a disorder of maladaptive immune and stromal interactions highlights opportunities to restore balance within this ecosystem and potentially alter disease course.