Figure 4. Macrophage-CLL cell interactions in the bone marrow are decreased on ibrutinib treatment.
A–B, Immunohistochemistry (original magnification 20 x) showing CD68+ (brown) macrophages in bone marrow specimens, inserts at 100 x magnification with macrophage extensions as CD68+ dots in close proximity of CLL cells, before start of treatment (PRE, A) and after eight weeks of ibrutinib treatment (8W, B). C, Schematic representation of macrophage-CLL interaction before and on ibrutinib. D, Semiquantitative assessment of CD68+ extensions among CLL cells in bone marrow specimens, 0 (no extensions) – 4 (max extensions), n=37 at PRE and 24W, n=7 at 48W, only patients with samples available at both PRE and 24W were included. See supplementary figure 3 for information on grading. Mean (±SEM). E, Mean (±SEM) percent of dead NLCs and CLL cells in co-culture after one week in 1 μM ibrutinib or control media, n=5. W: weeks on treatment, PRE: baseline. All statistical analyses were determined by Student’s paired t-test. Asterisks indicate degree of statistical significance compared to PRE: * P < .05 and *** P < .001.