Daunorubicin reductase activity in human normal lymphocytes, myeloblasts and leukemic cell lines

Abstract

To exploit the full potential of daunorubicin chemotherapy, it is necessary to understand its metabolism. We have shown previously that daunorubicin reduction in human liver is mediated by both aldehyde and ketone reductases. This study shows that this is also the case in normal blood cells. However, myeloblasts from AML patients show different pH profiles from those observed for normal lymphocytes. Human myeloid cell lines (KG1, ML1 and K562) accurately reflect the reductase heterogeneity seen in AML patients. This is in contrast to L1210 and P388 murine cell lines, which do not readily metabolize daunorubicin. When studying daunorubicin metabolism, it is important to use only cell lines that metabolize the drug because daunorubicin is extensively metabolized to daunorubicinol in AML patients. The use of human rather than rodent cell lines may provide useful information to increase our understanding of the in vivo situation.