Bone marrow stroma in childhood myelodysplastic syndrome: composition, ability to sustain hematopoiesis in vitro, and altered gene expression

• Published in: Leukemia research 2004-08, Vol.28 (8), p.831-844
• Main Authors: Borojevic, Radovan, Roela, Rosimeire A, Rodarte, Renato S, Thiago, Leandro S, Pasini, Fátima S, Conti, Fabiana M, Rossi, Maria Isabel D, Reis, Luiz F.L, Lopes, Luiz F, Brentani, M.Mitzi
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Alkaline Phosphatase - metabolism; Anemia, Refractory, with Excess of Blasts; Bone Marrow - metabolism; Bone Marrow - pathology; Bone marrow stromal cells; Case-Control Studies; cDNA array; Cell Differentiation; Child; Child, Preschool; Childhood myelodysplastic syndrome; Collagen Type IV - metabolism; Environment; Female; Fetal Blood - chemistry; Fetal Blood - metabolism; Fibroblasts - pathology; Fibronectins - metabolism; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematopoiesis; Humans; In Vitro Techniques; Infant; Laminin - metabolism; Male; Muscle, Smooth - metabolism; Muscle, Smooth - pathology; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - metabolism; Myelodysplastic Syndromes - pathology; Oligonucleotide Array Sequence Analysis; Osteoblasts - metabolism; Preleukemia; Stromal Cells - metabolism; Stromal Cells - pathology
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2003.11.019

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 α-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 α2-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.