Increased expression of fibroblast growth factor receptor 3 in CD34+ BCR-ABL+ cells from patients with chronic myeloid leukemia.
Previously, we showed that expression of myeloma-associated (proto)oncogene fibroblast growth factor receptor 3 (FGFR-3) is increased in white blood cells from patients with chronic myeloid leukemia (CML). The abnormal expression was returned back to the normal levels as soon as these patients reconstituted their hematopoiesis following transplantation of allogeneic peripheral blood stem cells. The aims of this study were: (1) to define population(s) of cells overexpressing FGFR-3, and (2) to determine the expression of FGFR-3 during the clinical course of the disease. We show that the vast majority of FGFR-3 transcripts as well as FGFR-3 protein arise from CD34+ BCR-ABL+ cells. Although increased levels of FGFR-3 were found in majority of late chronic phase patients treated with interferon alpha or hydroxyurea, the expression of FGFR-3 was always lowered following treatment with BCR-ABL tyrosine kinase inhibitor STI571. Compared to unstimulated cells, high levels of FGFR-3 were also identified in CD34+ cells from granulocyte colony-stimulating factor-mobilized blood stem cell harvests from healthy donors, suggesting a potential growth factor-dependent basis for elevated expression of FGFR-3 in CML. These findings have implications for the involvement of FGFR-3 in malignant hematopoiesis and depict FGFR-3 tyrosine kinase in CD34+ leukemic cells as a possible target for tyrosine kinase inhibitors.
Dvorak
P
P
Department of Molecular Embryology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Dvorakova
D
D
Doubek
M
M
Faitova
J
J
Pacholikova
J
J
Hampl
A
A
Mayer
J
J
D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*
D018952:Antigens, CD34; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017468:Receptors, Fibroblast Growth Factor; D016179:Granulocyte Colony-Stimulating Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D016044:Fusion Proteins, bcr-abl