title: Effect of stem cell factor on colony growth from acquired and constitutional (Fanconi) aplastic anemia.
abstract: The aim of this study was to evaluate the effect of stem cell factor (SCF) on the in vitro growth of bone marrow hematopoietic progenitors from patients with acquired severe aplastic anemia (AA) or Fanconi's anemia (FA). For this purpose, we studied 11 patients with acquired AA (5 at diagnosis, 6 after ALG treatment), 12 patients with FA, and nine normal controls. Bone marrow cells were plated in vitro for colony-forming unit granulocyte-macrophage (CFU-GM) (in the presence of granulocyte-macrophage colony-stimulating factor [GM-CSF]), and for burst-forming unit-erythroid (BFU-E) and CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM) colonies (in the presence of erythropoietin and interleukin-3 [IL-3]), with or without 20 ng/mL of SCF. In normal controls, SCF enhanced the growth of CFU-GM colonies from 103 to 263 (median), of BFU-E from 168 to 352, and of GEMM colonies from 6 to 38/10(5) cells plated. In patients with acquired AA, SCF induced a significant enhancement of BFU-E growth (8 to 29; P = .01) and allowed the formation of GEMM colonies that were not scored in baseline culture conditions (0 to 8; P = .01). CFU-GM growth was enhanced (4 to 20), but not significantly (P = .3). This was true both for patients at diagnosis and after antilymphocyte globulin treatment. By contrast, 10 of 12 FA patients grew no CFU-GM, BFU-E, or CFU-GEMM colonies, with or without SCF. In two FA patients (one transfusion-dependent and one transfusion-independent), an enhancement of CFU-GM and/or BFU-E was observed. The lack of response of hematopoietic progenitor cells from FA patients to GM-CSF+SCF or IL-3+SCF was not dependent on a defective expression of cytokine receptor messenger RNAs. Northern blot analysis showed in marrow cells from acquired AA and FA patients the presence of normal transcripts for alpha- and beta-chains of GM-CSF/IL-3 receptor and for c-kit protein. In conclusion, SCF promotes the in vitro growth of hematopoietic progenitors in patients with acquired AA, but not in patients with FA, pointing out the intrinsic nature of the defect in the latter disorder.
authors.affiliation: Divisione di Ematologia, Ospedale San Martino, Genova, Italy.
authors.forename: G P
authors.initials: GP
authors.lastname: Bagnara
authors.forename: P
authors.initials: P
authors.lastname: Strippoli
authors.forename: L
authors.initials: L
authors.lastname: Bonsi
authors.forename: M F
authors.initials: MF
authors.lastname: Brizzi
authors.forename: G C
authors.initials: GC
authors.lastname: Avanzi
authors.forename: F
authors.initials: F
authors.lastname: Timeus
authors.forename: U
authors.initials: U
authors.lastname: Ramenghi
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: J
authors.initials: J
authors.lastname: Tong
authors.forename: M
authors.initials: M
authors.lastname: Podesta
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D015152:Blotting, Northern; D001853:Bone Marrow / Q000473:pathology*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D003114:Colony-Forming Units Assay; D016572:Cyclosporine / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007165:Immunosuppression Therapy; D007621:Karyotyping; D008297:Male; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D019089:Stem Cell Factor
chemical_list: D000961:Antilymphocyte Serum; D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D012313:RNA; D016572:Cyclosporine