Thrombocytopenia with absent radii: Frequency of marrow megakarycyte progenitors, proliferative characteristics, and megakaryocyte growth and development factor responsiveness

Congenital thrombocytopenia with absent radii (TAR syndrome) is characteriz ed 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 patien ts and 6 normal controls, using optimally standardized megakaryocyte growth media incorporating interleukin-3, interleukin-6, stem cell factor, and gr anulocyte-monocyte colony-stimulating factor, with and without pegylated re combinant 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 (3-2 0 cells/colony) was observed in all patients in cultures without PEG-rHuMGD F, with a mean frequency of 8 (range 5-12) per 2.25 x 10(5) mononuclear cel ls plated (control mean 23; range 2-70). Identical cultures of marrow cells from patients and controls with added PEG-rHuMGDF produced more colonies p er dish (mean 17, range 8-23; control mean 30, range 6-62). Except for 1 ca se, however, patients' colonies in response to PEG-rHuMGDF remained smaller than those of controls. Two patients tested had higher plasma thrombopoiet in levels than 6 normal subjects. The findings demonstrate proliferative an d PEG-rHuMGDF-responsive megakaryocytic progenitors in TAR syndrome. The mo dest reduction in frequency of megakaryocyte progenitors and the suboptimal size of colonies in response to PEG-rHuMGDF are compatible with the report ed defective signal transduction in the c-mpl pathway in TAR syndrome.