CD146(+) bone marrow osteoprogenitors increase in the advanced stages of primary myelofibrosis.
CD146(+) bone marrow stromal cells have been recently recognized as clonogenic osteoprogenitors able to organize a complete hematopoietic microenvironment. In this study we used immunohistochemical analysis to investigate the contribution of CD146(+) bone marrow osteoprogenitors to the stromal remodeling occurring in the different stages of primary myelofibrosis. We found that CD146(+) cells sited at the abluminal side of the bone marrow vessels and branching among hematopoietic cells significantly increased in the advanced stages of primary myelofibrosis (p<0.001), paralleling the extent of fibrosis (rho=0.916, p<0.0001) and the microvascular density (r=0.883, p<0.0001). Coherently with a mural cell function, such cells also displayed smooth-muscle actin expression. Our data providing evidence of CD146(+) cell involvement in bone marrow stromal changes occurring in primary myelofibrosis are consistent with the capability of these cells to participate in fiber deposition, angiogenesis, and bone formation. They could also represent rationale for new therapies targeting the bone marrow stroma in primary myelofibrosis.
Tripodo
Claudio
C
Department of Human Pathology, University of Palermo, Palermo, Italy. tripodo@unipa.it
Di Bernardo
Andrea
A
Ternullo
Maria Paola
MP
Guarnotta
Carla
C
Porcasi
Rossana
R
Ingrao
Sabrina
S
Gianelli
Umberto
U
Boveri
Emanuela
E
Iannitto
Emilio
E
Franco
Giovanni
G
Florena
Ada Maria
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D051929:CD146 Antigen / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D055728:Primary Myelofibrosis / Q000378:metabolism* / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D051929:CD146 Antigen