title: Evidence for a multistep pathogenesis of a myelodysplastic syndrome.
abstract: Somatic cell genetic approaches utilizing the cellular mosaicism present in women heterozygous for glucose-6-phosphate dehydrogenase (G6PD) have provided information relevant to the pathogenesis of some neoplastic disorders. With these techniques, we studied a 61-year-old woman with a myelodysplastic syndrome. GdB/GdA heterozygosity was demonstrated in skin and cultured T lymphocytes, which exhibited both A and B type G6PD. In contrast, erythrocytes, platelets, granulocytes, and marrow nucleated cells displayed almost exclusively G6PD type B. In addition, 21 of 24 Epstein-Barr virus-transformed B lymphoblastoid lines that expressed a single immunoglobulin light chain showed only type B G6PD, suggesting that the stem cells involved by this disease were clonal and could differentiate to B lymphocytes as well as to mature granulocytes, erythrocytes , and platelets. Cultured skin fibroblasts and phytohemagglutinin-stimulated lymphocytes were karyotypically normal, but two independent abnormalities were found in marrow--47,XX, +8 and 46,XX,del(11)(q23). None of 14 type B G6PD lymphoblastoid lines analyzed in detail contained these karyotypic abnormalities, which strongly suggests that a visible chromosomal alteration is not the sole step in the development of this disease. We hypothesize that at least two events are involved in the pathogenesis of this patient's myelodysplasia: one causing proliferation of a clone of genetically unstable pluripotent stem cells and another inducing chromosomal abnormalities in its descendants.
mesh_terms: D001854:Bone Marrow Cells; D002472:Cell Transformation, Viral; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D007621:Karyotyping; D008875:Middle Aged; D011289:Preleukemia / Q000235:genetics*
chemical_list: D005954:Glucosephosphate Dehydrogenase