In vitro effect of stem cell factor on colony growth from acquired severe aplastic anemia.
In this study we review our present understanding of the effect of stem cell factor (SCF) on the in vitro growth of hemopoietic progenitors from patients with acquired severe aplastic anemia (SAA). We have run three separate sets of experiments. First, we have tested the expression of receptor mRNAs for granulocyte-macrophage colony stimulating factor/interleukin 3 (GM-CSF/IL-3) and for c-kit protein on bone marrow (BM) cells from SAA patients. Molecular analysis revealed the presence of normal transcripts for alpha and beta chains of GM-CSF/IL-3 receptor and for c-kit protein by Northern blot analysis. Second, we have tested the in vitro response to SCF of BM cells derived from 11 SAA patients: SCF induced a significant enhancement of erythroid burst forming unit (BFU-E) growth (8 to 29, p = 0.01) and allowed the formation of granulocyte/erythroid/macrophage/megakaryocyte (GEMM) colonies which were not scored in baseline culture conditions (0 to 8, p = 0.01). Granulocyte-macrophage colony forming unit (CFU-GM) growth was also enhanced (4 to 20, p = 0.3). This was true for patients both at diagnosis and after antilymphocyte globulin (ALG) treatment. We concluded that SCF can promote the in vitro growth of hemopoietic progenitors in patients with acquired SAA. Third, we have tested the response to SCF of peripheral blood (PB) hemopoietic progenitors collected from patients receiving in vivo long-term treatment with granulocyte CSF (G-CSF). When PB cells were plated directly in the presence of GM-CSF there was no colony formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacigalupo
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A
Divisione di Ematologia, Ospedale San Martino, Genova, Italy.
Piaggio
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G
Podestá
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Raffo
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MR
Tedone
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E
Sogno
G
G
Benvenuto
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F
Figari
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Grassia
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L
Bagnara
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GP
D000741:Anemia, Aplastic / Q000188:drug therapy / Q000473:pathology*; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007377:Interleukin-3 / Q000494:pharmacology; D010865:Pilot Projects; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D007166:Immunosuppressive Agents; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016185:Receptors, Interleukin-3; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases