New study on potential therapeutic approach for primary myelofibrosis (PMF)

A research team at the Institute for Cell and Tumor Biology at Uniklinik RWTH Aachen has increased the knowledge on a new promising strategy to slow the progression of the rare bone-marrow disease Primary Myelofibrosis (PMF), in which the marrow becomes fibrotic and blood-cell production is impaired.

In our study, we demonstrated that an inflammatory signalling axis between the blood-forming (haematopoietic) cells and the stromal cells of the bone marrow acts as a major driver of fibrosis. Treatment with the small-molecule Tasquinimod, or deletion of the alarmin protein S100A9 in haematopoietic cells, significantly reduced bone-marrow fibrosis and improved blood parameters in pre-clinical models.
Specifically, we found that in JAK2 V617F-mutant cells—a mutation characteristic of PMF—Tasquinimod decreased proliferative and mTORC signalling, enhanced apoptosis, and reversed the fibrotic reprogramming of megakaryocytes and monocytes. This, in turn, reduced activation of the stromal cell compartment.

Why does this matter? In PMF, fibrosis of the bone marrow microenvironment is a key factor in disease progression: the more scar tissue, the poorer the blood-cell output. Our approach targets the inflammatory cross-talk between haematopoietic and stromal cells rather than focusing on one cell type alone.
These findings increase the understanding of a novel therapeutic mechanism—interrupting the inflammation-stroma connection within the marrow. Further clinical studies will be needed to determine whether this approach can translate into patient benefit.

The original article is published under https://doi.org/10.1002/hem3.70179