One of the causes of acute myeloid leukemia (AML) resistance to conventional therapy is a de novo drug resistance of AML cells. This resistance associated with microenvironment of leukemic cells in bone marrow (interleukins, growth factors, CSFs). In multicellular aggregates resistance of AML primary cells and THP-1 cells to rh izTRAIL, etoposide, and sorafenib are increase. Disruption of cell-to-cell contact decreased resistance of THP-1 cells to rh izTRAIL, etoposide, and sorafenib. Disruption of cell-to-cell contact decreased resistance of primary AML cells to etoposide and sorafenib, but not to rh izTRAIL. We suppose that one of the causes of de novo AML drug resistance can be multicellular aggregations of AML cells in bone marrow.
This work was supported by grant of the Government of the Russian Federation №14.Z50.31.0028 and grant of the Russian Foundation of Basic Research №14-04-32183.