Unique human CD133 + leukemia cell line and its modulation towards a mesenchymal phenotype by FGF2 and TGFβ 1

Immunological features of GM‐490 cells, a new blood cell line from a patient with acute lymphoblastic leukemia, included lack of CD34, CD38, CD45, CD14, HLA‐DR, and lymphoid and myeloid markers and expression of CD29, CD36, CD44, CD54, CD71, CD105, and CD133. Molecular analysis indicated CD45 gene expression was absent but CD34 mRNA was present. GM‐490 cells constitutively produced fibronectin (FN), type III and traces of type I collagen, collagenases, glycosaminoglycans (GAG) and biglycan and betaglycan proteoglycans (PG) as well as FGF2 and TGFβ 1 . When FGF2 and/or TGFβ 1 were added to cells in vitro, they stimulated cell proliferation and differently modulated matrix production and growth factor receptor expression. Reverse transcription‐polymerase chain reaction (RT‐PCR) detection of transcripts encoding for osteocalcin and RUNX2 suggests GM‐490 cells differentiate towards the osteoblast pathway. GM‐490 cells expressed the low affinity nerve growth factor receptor (p75 LNGFR ), a somatic stem cell marker that is not detected in hematopoietic cells, leading to the hypothesis that GM‐490 has mesenchymal stem cell properties. The reciprocal modulating effects of FGF2 and TGFβ 1 on each other's receptors make the GM‐490 cell line a new model for investigating the relationship between these growth factors and their receptors in autocrine loops which are believed to sustain the malignant clone in hematological diseases. © 2005 Wiley‐Liss, Inc.