title: Endogenous FLT-3 ligand serum levels are associated with disease stage in patients with myelodysplastic syndromes.
abstract: Myelodysplastic syndromes (MDS) caused by a clonal hematopoietic stem cell disorder progress to either overt leukemia or cytopenia, which leads to lethal infection or bleeding. Although several clinical trials have attempted to reverse cytopenia by using hematopoietic growth factors (HGF), success has been limited due in part to a limited understanding of the role of HGF in MDS progression. The FLT3 ligand, which binds to and activates the FLT3 receptor, does not have a stimulatory effect on hematopoietic cells, but can synergize with other HGF to support the expansion of both immature and committed progenitors. Using ELISA technology we measured endogenous serum levels in 93 patients with MDS: 29 RA, 1 RARS, 31 RAEB, 23 RAEBt, 9 CMML. 48.3% of RA patients' sera had significantly elevated FLT3 ligand levels ranging from 404 to 5735 pg/ml, whereas none of the RAEB, RAEBt, or CMML patients sera had levels different from controls. No significant correlation was found between FLT3 ligand levels and peripheral blood counts, bone marrow cellularity, age, cytogenetic abnormalities, or survival. Our data suggest that FLT3 ligand levels can be upregulated early in the course of MDS, which may represent an appropriate response to a decreased number of normal progenitors, or alternatively a dysregulated HGF system.
authors.affiliation: Medizinische Universitätsklinik Innsbruck, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Zwierzina
authors.forename: J E
authors.initials: JE
authors.lastname: Anderson
authors.forename: I
authors.initials: I
authors.lastname: Rollinger-Holzinger
authors.forename: B
authors.initials: B
authors.lastname: Torok-Storb
authors.forename: V
authors.initials: V
authors.lastname: Nuessler
authors.forename: S D
authors.initials: SD
authors.lastname: Lyman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000097:blood / Q000473:pathology; D000754:Anemia, Refractory, with Excess of Blasts / Q000097:blood / Q000473:pathology; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000097:blood; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000150:complications / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology; D019089:Stem Cell Factor / Q000502:physiology; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3