Polycythemia vera. Increased expression of normal committed granulocytic stem cells in vitro after exposure of marrow to tritiated thymidine.
In previous studies of two patients with polycythemia vera (PV) and heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G-6-PD), only type A isoenzyme was found in non-lymphoid hematopoietic cells. However, some granulocytic and erythrocytic colonies grown in vitro had type B G-6-PD and therefore arose from presumably normal progenitors. In this study we exposed marrow cells from these same two patients to high-specific activity tritiated thymidine (3HTdR) before culture to kill cells actively synthesizing DNA. Individual granulocytic colonies were plucked and tested for G-6-PD after 14 d of culture. The frequency of type B colonies rose after exposure to 3HTdR from 8/101 to 11/36 in patient 1 and from 0/32 to 6/31 in patient 2 (P less than 0.003). No increase in the frequency of normal erythroid bursts after 3HTdR exposure was seen, implying that in PV, early granulopoiesis, and erythropoiesis are regulated differently. The results demonstrated that only type A granulocytic colonies, arising from the abnormal clone, were removed by the 3HTdR. In addition, for patient 2, statistical analysis indicated there was an absolute increase in normal granulocytic colonies detected in culture. Thus, PV clonal colony-forming units in culture (CFU-C) cycle more rapidly than do normal CFU-C and may suppress proliferation of normal CFU-C in vitro.
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D006098:Granulocytes / Q000473:pathology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics; D007958:Leukocyte Count; D010641:Phenotype; D011087:Polycythemia Vera / Q000097:blood* / Q000235:genetics; D013936:Thymidine / Q000494:pharmacology; D014316:Tritium
D007527:Isoenzymes; D014316:Tritium; D005954:Glucosephosphate Dehydrogenase; D013936:Thymidine