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

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

doi:10.1016/j.leukres.2003.11.019

« Previous Next »Leukemia Research
Volume 28, Issue 8 , Pages 831-844, August 2004

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

Radovan Borojevic
- Hospital Universitário Clementino Fraga Filho and Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
Rosimeire A Roela
- Disciplina de Oncologia, Departamento de Radiologia, Faculdade de Medicina da Universidade de Sao Paulo (LIM-24), Av. Dr Arnaldo, 455-sala 4112, CEP 01246-903 Sao Paulo, Brazil
- The authors have contributed equally to this study.
Renato S Rodarte
- Hospital Universitário Clementino Fraga Filho and Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
- The authors have contributed equally to this study.
Leandro S Thiago
- Hospital Universitário Clementino Fraga Filho and Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
Fátima S Pasini
- Disciplina de Oncologia, Departamento de Radiologia, Faculdade de Medicina da Universidade de Sao Paulo (LIM-24), Av. Dr Arnaldo, 455-sala 4112, CEP 01246-903 Sao Paulo, Brazil
Fabiana M Conti
- Hospital Universitário Clementino Fraga Filho and Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
Maria Isabel D Rossi
- Hospital Universitário Clementino Fraga Filho and Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil
Luiz F.L Reis
- Instituto Ludwig, São Paulo, Brazil
Luiz F Lopes
- Departamento de Pediatria do Hospital do Câncer A.C. Camargo, Brazil
M.Mitzi Brentani
- Disciplina de Oncologia, Departamento de Radiologia, Faculdade de Medicina da Universidade de Sao Paulo (LIM-24), Av. Dr Arnaldo, 455-sala 4112, CEP 01246-903 Sao Paulo, Brazil
- Corresponding author. Tel.: +55-11-30667488; fax: +55-11-30826580.

Received 8 September 2003; accepted 24 November 2003.

Abstract

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.

Keywords: Childhood myelodysplastic syndrome, Bone marrow stromal cells, cDNA array, Gene expression, Environment, Hematopoiesis