Leukaemic and Bone Marrow Stromal Cells Alter Cytarabine Genotoxicity and Cytotoxicity in Favour of Disease

Resistance to therapy remains one of the greatest challenges in the management of the blood and bone marrow (BM) disorder, acute myeloid leukaemia (AML). This study aimed to investigate how leukaemic and BM stromal cells contribute to altered chemo-sensitivity; with particular interest in genotoxicity protection of leukaemic cells and sensitisation of the supportive BM. AML cells (HL-60 and K562) were mono-cultured or cocultured with a stromal (HS-5) cell line using trans-well inserts, prior to treatment with a physiological dose of cytarabine (25 µM); standard AML induction therapy. Toxicity protection and sensitisation were determined by genotoxicity (micronucleus/alkaline comet) assays, viability (dye exclusion), chemo-sensitivity (bacterial bioluminescent biosensor) and proliferation (CFSE fluorescence). Leukaemic-stromal co-culture altered both cell types in favour of disease progression. HS-5 significantly reduced micronuclei formation (4.72/3.45%; p