Stromal SPARC contributes to thedetrimental fibrotic changes associated with myeloproliferation whereas itsdeficiency favors myeloid cell expansion.

Michela Giuliano, Carla Guarnotta, Giovanni Franco, Claudio Tripodo, Giuseppe Calvaruso, Ada Maria Florena, Matilde Cacciatore, Marika Sciandra, Stefano A. Pileri, Sabina Sangaletti, Claudia Chiodoni, Pier P. Piccaluga, Silvia Miotti, Alessandra Carè, Attilio Orazi, Katia Scotlandi, Mario P. Colombo

Risultato della ricerca: Articlepeer review

30 Citazioni (Scopus)

Abstract

In myeloid malignancies, the neoplastic clone outgrows normal hematopoietic cells toward BM failure. This event is also sustained by detrimental stromal changes, such as BM fibrosis and osteosclerosis, whose occurrence is harbinger of a dismal prognosis. We show that the matricellular protein SPARC contributes to the BM stromal response to myeloproliferation. The degree of SPARC expression in BM stromal elements, including CD146(+) mesenchymal stromal cells, correlates with the degree of stromal changes, and the severity of BM failure characterizing the prototypical myeloproliferative neoplasm primary myelofibrosis. Using Sparc(-/-) mice and BM chimeras, we demonstrate that SPARC contributes to the development of significant stromal fibrosis in a model of thrombopoietin-induced myelofibrosis. We found that SPARC deficiency in the radioresistant BM stroma compartment impairs myelofibrosis but, at the same time, associates with an enhanced reactive myeloproliferative response to thrombopoietin. The link betwen SPARC stromal deficiency and enhanced myeloid cell expansion under a myeloproliferative spur is also supported by the myeloproliferative phenotype resulting from the transplantation of defective Apc(min) mutant hematopoietic cells into Sparc(-/-) but not WT recipient BM stroma. Our results highlight a complex influence of SPARC over the stromal and hematopoietic BM response in myeloproliferative conditions.
Lingua originaleEnglish
pagine (da-a)3541-3554
Numero di pagine14
RivistaBlood
Volume120
Stato di pubblicazionePublished - 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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