title: Thrombocytopenia with absent radii: frequency of marrow megakaryocyte progenitors, proliferative characteristics, and megakaryocyte growth and development factor responsiveness.
abstract: Congenital thrombocytopenia with absent radii (TAR syndrome) is characterized by defective thrombopoiesis and bleeding in early infancy. To determine the frequency and responsiveness to cytokines of megakaryocyte progenitors (CFU-Meg) in TAR syndrome, the authors studied marrow samples from 3 patients and 6 normal controls, using optimally standardized megakaryocyte growth media incorporating interleukin-3, interleukin-6, stem cell factor, and granulocyte-monocyte colony-stimulating factor, with and without pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). CFU-Meg was identified with a specific staining system utilizing monoclonal antibodies to glycoprotein IIb/IIIa. Growth of small CFU-Meg colonies (3-20 cells/colony) was observed in all patients in cultures without PEG-rHuMGDF, with a mean frequency of 8 (range 5-12) per 2.25 x 10(5) mononuclear cells plated (control mean 23; range 2-70). Identical cultures of marrow cells from patients and controls with added PEG-rHuMGDF produced more colonies per dish (mean 17, range 8-23; control mean 30, range 6-62). Except for 1 case, however, patients' colonies in response to PEG-rHuMGDF remained smaller than those of controls. Two patients tested had higher plasma thrombopoietin levels than 6 normal subjects. The findings demonstrate proliferative and PEG-rHuMGDF-responsive megakaryocytic progenitors in TAR syndrome. The modest reduction in frequency of megakaryocyte progenitors and the suboptimal size of colonies in response to PEG-rHuMGDF are compatible with the reported defective signal transduction in the c-mpl pathway in TAR syndrome.
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, Ontario, Canada.
authors.forename: A H
authors.initials: AH
authors.lastname: al-Jefri
authors.forename: Y
authors.initials: Y
authors.lastname: Dror
authors.forename: J B
authors.initials: JB
authors.lastname: Bussel
authors.forename: M H
authors.initials: MH
authors.lastname: Freedman
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D011884:Radius / Q000002:abnormalities*; D013577:Syndrome; D013921:Thrombocytopenia / Q000151:congenital / Q000473:pathology*; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D013926:Thrombopoietin