Effect of differentiating agents on interferon-gamma (INF-gamma) level in leukemic cells propagated ex-vivo

Leukemia is a type of cancer that starts in the bone marrow. The anticancer drugs used in the treatment of patients suffering from the disease have many side effects due to their toxicity. This fact has prompted researchers to search for other agents instead of, or in combination with, these anticancer drugs. Differentiating agents (DAs) including Na-Butyrate (NaBu), trans-retinoic acid (TRA), dibutyryl- cAMP (Bu-cAMP) and many others have been used for this purpose.

In this investigation, we studied 120 patients with acute myeloid leukemia (AML),presenting to the Oncology Institute of Tanta, Egypt. We studied the effect of some differentiating agents (DAs)mainly Na-Butyrate (Na-Bu., 1mM), trans-retinoic acid (TRA, l micro M) and dibutyryl-cAMP (Bu-cAMP, lmM) on the morphology of leukemia cells propagated ex-vivo for 3 and 6 days. We also studied the level of interferon- gamma and its release in the conditioned media of the leukemic cells compared to normal leukocytes.

The results revealed that DAs enhanced the conversion of the immature granulocytes into mature ones clearly at 6 days of treatment when we used the agents in combination. The results also showed that statistically significant elevation (p<0.001) of interferon- gamma level was found to be in the conditioned media of the treated leukemic cells (3 and 6 days) using the previously mentioned agents alone or in combination; that could reach almost the level in the cultured media of normal leukocytes.

In conclusion, this work could highlight the possibility of using DAs as a novel complementary therapy in the management of acute myeloid leukemia (AML) via the activation of the immune surveillance of patients suffering from AML through raising the interferon- gamma level. Further work is recommended to use DAs in clinical trials with and without conventional anticancer drugs for the management of patient with AML.