Endogenous Tumor Necrosis Factor and Doxorubicin Sensitivity in Leukemic Patients

Sensitivity to doxorubicin (DOX) and expression of intracellular endogenous TNF (enTNF) or manganous superoxide dismutase (MnSOD) activity were found to be inversely correlated in leukemic cells from 19 patients (6 acute lymphoblastic leukemia, 13 acute myeloblastic leukemia). In a case with acquired resistance to chemotherapy which included DOX, enTNF expression and MnSOD activity were increased. Furthermore, in 14 cases treated with a regimen including an anthracycline, 4 cases which failed to respond to chemotherapy showed relatively high amounts of enTNF expression. After TNF antisense cDNA was transfected into leukemic cells isolated from 5 patients, sensitivity of transfectants to DOX increased 1.4- to 2.5-fold. Overall, we found enTNF to act as a resistance factor against DOX in leukemia which may predict response to DOX.