Establishment and characterization of long-term cultures derived from primary acute myeloid leukemia cells for HDAC inhibitor research

Abstract

Histone deacetylase (HDAC) inhibitors are promising drugs. These agents lead to growth inhibition, cell cycle arrest, premature senescence, and apoptosis of malignant cells. Aim of our studies was to determine the efficacy of HDAC inhibitors on the clinically most relevant population of human leukemic progenitor cells in vitro. We here present stroma-free long-term cultures (LTC) of primary acute myeloid leukemia (AML) cells as a useful system for drug sensitivity testing in functional assays. AML-LTC are established by isolating mononuclear cells from peripheral blood samples of AML patients followed by selection of CD34+ progenitor cells. AML-LTC cells can be maintained in liquid culture supplemented with cytokines and utilized for in vitro analyses to assess proliferation, apoptosis, expression of surface proteins or intracellular proteins and signal transduction, respectively.