Bone marrow stroma in childhood myelodysplastic syndrome: composition, ability to sustain hematopoiesis in vitro, and altered gene expression.
We studied bone marrow stromal cell cultures from patients with childhood myelodysplastic syndromes (MDS, refractory anemia with excess of blasts, RAEB) and from matched normal donors. Stromal cell monolayers were characterized as myofibroblasts by the expression of smooth muscle alpha-actin, collagen IV, laminin and fibronectin. When normal cord blood cells were plated onto myelodysplastic stromas, a pathologic cell differentiation was observed, indicating altered myelosupportive properties. cDNA array analysis showed that patient stromas expressed increased levels of thrombospondin-1, collagen-I alpha2-chain, osteoblast-specific factor-2 and osteonectin, indicating the presence of increased osteoblast content, as confirmed by enhanced alkaline phosphatase synthesis. Alterations in the myelodysplastic stroma environment might contribute to abnormal hematopoiesis in this pathology.
Borojevic
Radovan
R
Hospital Universitário Clementino Fraga Filho and Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
Roela
Rosimeire A
RA
Rodarte
Renato S
RS
Thiago
Leandro S
LS
Pasini
Fátima S
FS
Conti
Fabiana M
FM
Rossi
Maria Isabel D
MI
Reis
Luiz F L
LF
Lopes
Luiz F
LF
Brentani
M Mitzi
MM
D000199:Actins / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000754:Anemia, Refractory, with Excess of Blasts; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007797:Laminin / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000378:metabolism; D011289:Preleukemia; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*
D000199:Actins; D024141:Collagen Type IV; D005353:Fibronectins; D007797:Laminin; D000469:Alkaline Phosphatase