2. Academic Validation
  3. CD44 Participates to Extramedullary Haematopoiesis Onset by Mediating the Interplay Between Monocytes and Haematopoietic Stem Cells in Myelofibrosis

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

  • J Cell Mol Med. 2025 Jul;29(14):e70720. doi: 10.1111/jcmm.70720.
Margherita Mirabile 1 2,  Camilla Tombari 1 2,  Anita Neroni 1 3,  Lara Tavernari 1 2,  Ruggiero Norfo 1 2,  Elisa Bianchi 1 3,  Monica Maccaferri 4,  Barbara Mora 5,  Sandra Parenti 1 2,  Chiara Carretta 1 2,  Matteo Bertesi 1 3,  Marica Malerba 1 3,  Elisa Papa 1 3,  Luca Fabbiani 6,  Niccolò Bartalucci 7 8,  Paola Guglielmelli 7 8,  Leonardo Potenza 4 9,  Lorena Losi 6,  Francesco Passamonti 5 10,  Enrico Tagliafico 9 11,  Mario Luppi 4 9,  Sebastiano Rontauroli 1 2,  Alessandro Maria Vannucchi 7 8,  Rossella Manfredini 1 2,  MYNERVA (Myeloid NEoplasms Research Venture AIRC) investigators
Affiliations

Affiliations

  • 1 Interdepartmental Centre for Stem Cells and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • 2 Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • 3 Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • 4 Hematology Unit, Department Oncology and Hematology, Modena University Hospital, Modena, Italy.
  • 5 Ospedale Maggiore Policlinico, Milan, Italy.
  • 6 Pathology Unit, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • 7 CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, University of Florence, AOU Careggi, Florence, Italy.
  • 8 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
  • 9 Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • 10 University of Milan, Milan, Italy.
  • 11 Diagnostic Hematology and Clinical Genomics Unit, Department of Laboratory Medicine, Modena University Hospital, Modena, Italy.
PMID: 40690545 DOI: 10.1111/jcmm.70720
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.

Keywords

CD44; cell migration; extramedullary haematopoiesis; hyaluronic acid; myelofibrosis; osteopontin.

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