In vitro restoration of polyclonal hematopoiesis in a chronic myelogenous leukemia after in vitro treatment with 4-hydroperoxycyclophosphamide.
Bone marrow cells of a 45-year-old female with Philadelphia chromosome (Ph1)-positive, early-phase chronic myelogenous leukemia (CML), who was heterozygous for the glucose-6-phosphate dehydrogenase (G6PD) locus, were pretreated in vitro with 4-hydroperoxycyclophosphamide (4-HC) and tested for G6PD activity in several colony formation assays and for karyotypic abnormalities. All cells within the mixed (CFU-GEMM), the erythroid burst (BFU-E), and the granulocyte-macrophage (CFU-GM) colonies expressed type A and type B G6PD activity and a normal karyotype, whereas untreated cells expressed type A G6PD and the Ph1 chromosome. This reversal of G6PD activity type and the disappearance of the Ph1 chromosome in colonies grown from 4-HC-treated cells indicate that this cytotoxic agent spares a residual normal stem cell population in bone marrow cells of early-phase CML patients. This finding, in turn, suggests a therapeutic approach in CML based on in vitro chemotherapy of autologous bone marrow grafts.
D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006579:Heterozygote; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008875:Middle Aged
D003520:Cyclophosphamide; D005954:Glucosephosphate Dehydrogenase; C011272:perfosfamide