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 Apcmin 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3541-3554 |
| Number of pages | 14 |
| Journal | Blood |
| Volume | 120 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Oct 25 2012 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion. / Tripodo, Claudio; Sangaletti, Sabina; Guarnotta, Carla; Piccaluga, Pier P.; Cacciatore, Matilde; Giuliano, Michela; Franco, Giovanni; Chiodoni, Claudia; Sciandra, Marika; Miotti, Silvia; Calvaruso, Giuseppe; Carè, Alessandra; Florena, Ada M.; Scotlandi, Katia; Orazi, Attilio; Pileri, Stefano A.; Colombo, Mario P.
In: Blood, Vol. 120, No. 17, 25.10.2012, p. 3541-3554.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion
AU - Tripodo, Claudio
AU - Sangaletti, Sabina
AU - Guarnotta, Carla
AU - Piccaluga, Pier P.
AU - Cacciatore, Matilde
AU - Giuliano, Michela
AU - Franco, Giovanni
AU - Chiodoni, Claudia
AU - Sciandra, Marika
AU - Miotti, Silvia
AU - Calvaruso, Giuseppe
AU - Carè, Alessandra
AU - Florena, Ada M.
AU - Scotlandi, Katia
AU - Orazi, Attilio
AU - Pileri, Stefano A.
AU - Colombo, Mario P.
PY - 2012/10/25
Y1 - 2012/10/25
N2 - 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 Apcmin 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.
AB - 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 Apcmin 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.
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U2 - 10.1182/blood-2011-12-398537
DO - 10.1182/blood-2011-12-398537
M3 - Article
VL - 120
SP - 3541
EP - 3554
JO - Blood
JF - Blood
SN - 0006-4971
IS - 17
ER -