CLL cells cultured on marrow stromal cells or nurselike cells become partially resistant to ABT-737. (A) Bone marrow stromal cells secrete soluble factors and express matrix proteins that have the potential to traffic CLL to the bone marrow and promote their survival. CLL cells, from 2 representative different patients, cultured with the OP-9 bone marrow stromal cell line for 5 days (○) demonstrated a greater resistance to a range of ABT-737 concentrations than either freshly isolated CLL cells (♦) or CLL cells incubated for 5 days in the absence of OP-9 cells (●), although significant inter-individual variation in the degree of resistance was observed. Where the resistance to ABT-737 was greatest, as with cells from patient 1, there was substantial up-regulation of the prosurvival proteins, BCL-X_L, BCL2A1, and MCL1, but no or lower expression of the prosurvival proteins in patients with lower resistance to ABT-737 (data not shown). (B) Similarly, nurselike cells, a subset of monocytes derived from the blood of CLL patients, attract CLL cells and render them less sensitive to drug-induced apoptosis. After 14 days in culture, CLL cells from some patients (patient 3) associated with their own nurselike cells and were markedly resistant to ABT-737 (○) compared with freshly isolated CLL cells from the same patient (●). However, significant variation was observed with nurselike cells from different patients (see patient 4).