title: The effect of thrombopoietin on erythroid progenitors in Diamond-Blackfan anemia.
abstract: Diamond-Blackfan anemia (DBA) is a rare congenital red blood cell aplasia. Usually, erythropoiesis in vitro is defective, and decreased numbers of erythroid progenitors are found in colony assays performed with bone marrow cells. Recently, some investigators showed that thrombopoietin (TPO) also works on common multipotent progenitor cells and stimulates erythropoiesis. We examined the effect of TPO together with erythropoietin (EPO), stem cell factor (SCF), and/or interleukin-3 (IL-3) on erythroid burst-forming units (BFU-E) of bone marrow nonadherent mononuclear cells from 2 patients with DBA using a serum-free culture system. Very few BFU-E appeared in cultures containing EPO alone. Adding IL-3, SCF, or both to cultures containing EPO induced an increase in the number of BFU-E. When TPO was added to cultures containing EPO and IL-3, SCF, or both, the number of BFU-E further increased. Especially in patient 2, BFU-E formation was grossly equal to that in normal controls. We conclude that TPO enhances bone marrow erythropoiesis in patients with DBA in the presence of EPO and SCF and/or IL-3. The data raise the possibility of the combination of TPO and SCF as a therapeutic agent in DBA.
authors.affiliation: Department of Pediatrics, Kansai Medical University, Osaka, Japan. kawasaki@takii.kmu.ac.jp
authors.forename: Hirohide
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Takahide
authors.initials: T
authors.lastname: Nakano
authors.forename: Urara
authors.initials: U
authors.lastname: Kohdera
authors.forename: Yohnosuke
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000473:pathology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D016022:Case-Control Studies; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D007377:Interleukin-3 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D013926:Thrombopoietin