Flow cytometric determination with bromodeoxyuridine/DNA assay of sensitivity of S-phase cells to cytosine arabinoside in childhood acute lymphoblastic leukemia.
The percentages of S-phase cells in leukemic and normal bone marrow cells and their sensitivity to cytosine arabinoside (Ara-C) were determined by in-vitro bromodeoxyuridine (BrdUrd)/DNA analysis in children with acute lymphoblastic leukemia. The lymphoblasts during relapse showed a higher proliferating activity than at the time of the diagnosis. The sensitivity of S-phase cells to Ara-C was measured by the percentages of the residual S-phase cells capable of incorporating BrdUrd after incubation with various concentration of Ara-C (1 ng-10 micrograms/ml). A constant dose response was found in the normal bone marrow cells of disease-free children who were in complete remission with a marked reduction of the S-phase population at a concentration of 100 ng/ml. In the leukemic bone marrow cells, in contrast, there was a wide variation in sensitivity to Ara-C. The sensitivity did not correlate with the proliferating activity of leukemic cells. In two patients, there was a good correlation between in-vitro sensitivity and clinical response to Ara-C.
Katano
N
N
Department of Pediatrics, Aichi Medical University, Japan.
Tsurusawa
M
M
Niwa
M
M
Fujimoto
T
T
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells; D001973:Bromodeoxyuridine / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000494:pharmacology* / Q000627:therapeutic use; D004247:DNA / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007399:Interphase / Q000187:drug effects*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology*
D000911:Antibodies, Monoclonal; D003561:Cytarabine; D004247:DNA; D001973:Bromodeoxyuridine