Cell Aggregation Increases Drug Resistance of Acute Myeloid Leukemia Cells

One of the main reasons for the low efficiency of therapy of acute myeloid leukemia is drug resistance of leukemic cells. Microenvironment plays a major role in the forming of leukemic cell drug resistance phenotype. Studies of the mechanisms of the microenvironment-mediated drug resistance is important to identify new pharmacological targets for the acute myeloid leukemia therapy. We studied the role of cell aggregation in the drug resistance of leukemic cells. We showed that in multicellular aggregates resistance of acute myeloid leukemia cells THP-1 to bortezomib, doxorubicin and fludarabine was increased. In multicellular aggregates of THP-1 with increased drug resistance cell proliferating activity was unchanged, while the intracellular level of anti-apoptotic protein Bcl-2 was increased. Inhibition of THP-1 cells aggregation prevented the drug resistance. This work demonstrates the involvement of cell aggregation in the formation of drug resistance phenotype in leukemic cells.