title: Anomalous plasma concentrations and impaired secretion of growth factors in Fanconi's anemia.
abstract: In Fanconi's anemia, which is known to be an autosomal recessive Mendelian trait with four complementary groups. In addition to stunning phenotypic variation at clinical and cellular levels, aplastic pancytopenia is a common feature. Since either an early block of differentiation in stem cells or their insufficient support by stromal functions could be an underlying factor, levels of stem cell factor (SCF) and cytokines have been measured in blood and in supernatants of monocytes after stimulation with granulocyte-macrophage colony stimulating factor (GM-CSF). In two of three FA patients, no GM-CSF was detectable, and simultaneously SCF was decreased to 8% and 15% of normal values. The combination of low SCF and GM-CSF may be implied in the pathogenesis of marrow aplasia, since comparison with W/Sl mice shows that impairment of the SCF/c-kit function alone has different effects. Also, this explains that treatment with GM-CSF in a recent study enhanced only leukogenesis and not all three lineages. In the third patient, both factors were normal, and here a different mechanism may act. In all three FA patients, interleukin 6 (IL-6) production in stimulated monocytes was decreased, which may hamper immune defense of infections in a nonspecific way.
authors.affiliation: Institut de Recherche en Hématologie et Transfusion, Hôpital du Hasenrain, Mulhouse, France.
authors.forename: E
authors.initials: E
authors.lastname: Wunder
authors.forename: B T
authors.initials: BT
authors.lastname: Mortensen
authors.forename: F
authors.initials: F
authors.lastname: Schilling
authors.forename: P R
authors.initials: PR
authors.lastname: Hénon
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D005199:Fanconi Anemia / Q000097:blood*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood* / Q000378:metabolism; D016298:Hematopoietic Cell Growth Factors / Q000097:blood* / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000097:blood* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D019089:Stem Cell Factor
chemical_list: D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D015850:Interleukin-6; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor