# CD44 Participates to Extramedullary Haematopoiesis Onset by Mediating the Interplay Between Monocytes and Haematopoietic Stem Cells in Myelofibrosis

## TL;DR

This study shows that CD44 helps monocytes and blood stem cells move to the spleen in myelofibrosis, causing extramedullary blood production.

## Contribution

The study reveals CD44's role in mediating monocyte-HSPC interactions that drive extramedullary haematopoiesis in myelofibrosis.

## Key findings

- CD44 inhibition reduces monocyte and HSPC migration in an in vitro model.
- MF monocytes produce more hyaluronic acid, promoting HSPC migration.
- Ruxolitinib reduces spleen size but does not stop EMH onset.

## Abstract

Extramedullary haematopoiesis (EMH) refers to blood generation outside of the bone marrow (BM). In Myelofibrosis (MF), a myeloproliferative neoplasm, the disruption of BM microenvironment promotes haematopoietic stem and progenitor cells (HSPCs) mobilisation, resulting in the onset of EMH in the spleen, and then in splenomegaly. Although JAK2 inhibitors have a good efficacy in reducing splenomegaly, the presence of a significant proportion of non‐responder patients underlines the need to explore the cellular mechanisms responsible for the EMH onset. In a MF mouse model, Ruxolitinib induces a reduction in spleen volume but does not affect EMH. CD44 inhibition successfully reduces monocyte and HSPC migration in an in vitro extravasation model. Strikingly, MF monocytes are more effective in promoting HSPC migration through the production of hyaluronic acid. Collectively, our results demonstrate that CD44 regulates the migration of monocytes that are crucial for the onset of EMH in MF patients, as they produce CD44 ligands recruiting HSPCs from the BM.