Still a burning question: the interplay between inflammation and fibrosis in myeloproliferative neoplasms

Abstract

Purpose of review: Bone marrow fibrosis is the progressive replacement of blood-forming cells by reticulin fibres, caused by the acquisition of somatic mutations in hematopoietic stem cells. The molecular and cellular mechanisms that drive the progression of bone marrow fibrosis remain unknown, yet chronic inflammation appears to be a conserved feature in most patients suffering from myeloproliferative neoplasms.

Recent findings: Here, we review recent literature pertaining to the role of inflammation in driving bone marrow fibrosis, and its effect on the various hematopoietic and nonhematopoietic cell populations.

Summary: Recent evidence suggests that the pathogenesis of MPN is primarily driven by the hematopoietic stem and progenitor cells, together with their mutated progeny, which in turn results in chronic inflammation that disrupts the bone marrow niche and perpetuates a disease-permissive environment. Emerging data suggests that specifically targeting stromal inflammation in combination with JAK inhibition may be the way forward to better treat MPNs, and bone marrow fibrosis specifically.

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FIGURE 1

Inflammation and fibrosis during myeloproliferative neoplasm progression. (a) Cell interactions in the bone marrow microenvironment. Inflammatory cues precede and/or result from MPN-driving mutations. Monocytes and megakaryocytes fuel stromal inflammation, early during MPN progression. MSCs undergo a transcriptional reprogramming and eventually differentiate into fibrosis-driving myofibroblasts. (b) Scheme of putative kinetics and correlation of inflammation and fibre deposition during MPN. Elevation of inflammation occurs before overt fibrosis. This early inflammatory context accelerates disease progression and provides a window of opportunity for therapeutic intervention. MPN, myeloproliferative neoplasm; MSCs, mesenchymal stromal cells.