In order to improve understanding of the effects of chemotherapy on human leukemic and normal bone marrow cells, in vitro cell-kill by chemotherapeutic agents will be quantitatively studies using a cell-culture method; This is the newly developed culture method with the unique feature of daily feeding for assay of clonogenic human leukemic cells (L-CFU), This can also be used for the assay of normal myeloid precursor cells (CFU-C). Bone marrow cells will be exposed to the graded doses of the chemotherapeutic agents in vitro for 1 hour in an incubator, and then washed free of the drugs before culture for the surviving fractions of L-CFU or CFU-C. From the dose survival curves thus obtained, quantitative parameters to express chemotherapy sensitivity and synergism of combination chemotherapy will be derived. Using these parameters as guidelines, more effective in vitro chemotherapy regimen will be searched systematically. Also in vitro parameters will be correlated with in vivo response to chemotherapy to find reliable in vitro predictive systems for in vivo response. Growth regulation of leukemic cells will also be studied in vitro.
NIH ExPorter
NIH ExPorter