Analysis of heterogeneity in daunorubicin uptake by human leukemia cells using laser flow cytometry

Heterogeneity in daunorubicin uptake by leukemic blast cells obtained from the bone marrow of 16 patients with acute leukemia (10 acute nonlymphocytic leukemia and 6 acute lymphocytic leukemia) was determined by laser flow cytometry following drug treatment in vitro for 1 hr. Fluorescence profiles of cellular anthracycline levels in the various samples indicated a marked heterogeneity in daunorubicin uptake and the range of detectable drug fluorescent cells was 34%-99%. A retrospective analysis of disease outcome in these patients who were treated with a daunorubicin or doxorubicin containing induction regimen indicated the following: (a) 8 of 11 patients who entered complete remission had greater than 80% of leukemic blast cells accumulating detectable amounts of daunorubicin; and (b) 3 of 4 patients who did not respond to chemotherapy had less than 40% of the leukemic blast cells accumulating detectable amounts of daunorubicin. These results suggest that laser flow cytometry may be useful in determining qualitative and quantitative differences in daunorubicin levels in heterogeneous tumor cell populations.