# Chronic Inflammation in Primary Myelofibrosis: In-Depth Insights Into Pathogenesis and Promising Anti-Inflammatory Therapeutic Strategies

## TL;DR

This paper reviews the role of chronic inflammation in primary myelofibrosis and explores new anti-inflammatory treatment strategies.

## Contribution

The paper integrates recent findings, especially from single-cell RNA sequencing, to guide future therapeutic strategies for primary myelofibrosis.

## Key findings

- Chronic inflammation in PMF is driven by inflammatory mediators, oxidative stress, and immune dysregulation.
- Single-cell RNA sequencing reveals regulatory mechanisms of inflammation and interactions between hematopoietic and stromal cells.
- Anti-inflammatory therapies targeting immune cells and cytokines show promise for PMF treatment.

## Abstract

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm (MPN) stemming from hematopoietic stem and progenitor cells (HSPCs), frequently associated with mutations in Janus kinase signal transducer (JAK2), calreticulin (CALR), or thrombopoietin receptor (MPL). Characterized by intricate clonality and dysregulated inflammation, PMF leads to heightened morbidity, mortality, and an elevated risk of leukemic transformation. The inflammatory state in PMF results from the convoluted interplay of excessive inflammatory mediator production, heightened oxidative stress, and immune system dysregulation. These factors fuel the expansion of the myeloproliferative clone, accelerate disease progression toward leukemia, and contribute to bone marrow (BM) fibrosis by acting on BM stromal cells. This review comprehensively integrates recent research findings, especially those from single-cell RNA sequencing, to identify the sources and regulatory mechanisms of inflammatory mediator overproduction, oxidative stress, and immune system dysregulation in PMF. It also elaborates on the key cytokines and pathways governing the interaction between malignant hematopoietic cells and BM stromal cells. By providing a comprehensive perspective, this review aims to guide future research on cellular and molecular targets within the hematopoietic niche and explore therapeutic approaches targeting immune cells and cytokines for PMF treatment. The potential of anti-inflammatory therapies in the clinical management of PMF is also highlighted.