Sensitivity of myeloid progenitor cells in healthy subjects and patients with chronic myeloid leukemia to chemotherapeutic agents.
The different sensitivity of myeloid progenitor cells (CFUc) to chemotherapeutic agents was measured with an in vitro clonogenic assay. Normal marrow and peripheral blood CFUc and blood CFUc obtained from patients with chronic myelogenous leukemia (CML) were tested for their sensitivity to medications used currently in the management of CML. The drugs tested were adriamycin, L-asparaginase, busulfan, beta-cytosine arabinoside (Ara-C), daunorubicin, hydroxyurea, melphalan, and thioguanine. CML CFUc were significantly more sensitive to Ara-C [drug dose required for 90% inhibition of CFUc growth (LD90) = 0.015 +/- 0.003 microgram/ml] than were normal CFUc (LD90 = 0.038 +/- 0.009 microgram/ml). A shift to enhanced sensitivity to L-asparaginase was detected in patients studied sequentially who entered blast transformation during this study. In vitro and in vivo pharmacokinetic data are compared.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012044:Regression Analysis
D000970:Antineoplastic Agents; D003561:Cytarabine