Effect of fatty acid oxidation substrates on DEX-mediated death. (A) Adipocytes and ACM were prepared as described in the Materials and methods; 6 × 10⁶ CLL cells were cocultured with (A) OP-9–derived adipocytes or (B) in ACM (with or without heat inactivation) in the presence or absence of DEX for 48 hours. Specific death was then determined by staining with 7AAD and flow cytometric analysis. (C) CLL cells from 10 different patients were cultured with or without DEX in the presence or absence of low-density lipoproteins (LDLs) or very-low-density lipoproteins (VLDLs) (1:200 and 1:100 final concentrations, respectively). The averages and standard errors of specific death results for each treatment are shown. (D) CLL cells from 15 individual patients were cultured with or without DEX in the presence or absence of propionic acid (1 mM), an odd-numbered fatty acid that provides both acetyl-CoA and succinate to support the TCA cycle. Percentages of viable 7AAD⁻ cells were measured 48 hours later by flow cytometry. Specific death is the difference between the percentages of 7AAD⁺ cells in control and DEX-treated samples. (E) Mitochondrial membrane potentials of DEX-treated CLL cells supplied with propionic acid were determined after 18 hours by staining with DiOC₆(3) and flow cytometric analysis. As a control, DEX-treated CLL cells were also treated with the GR antagonist mifepristone (1 μM). An example is shown. (F) Summary of DiOC₆(3) MFI measurements for 8 different patient samples, indicating that propionic acid and mifepristone both restore mitochondrial membrane potential in DEX-treated CLL cells. **P < .01; *P < .5.