Figure 4.
CIC is associated with prior therapies, increases with in vivo BTKi therapy and ex vivo ibr exposure. (A) Number of internalized cells were quantified for 43 CLL cases. Four to 6 fields were examined per sample. Each dot represents the average number of CIC per field per sample of 4 to 6 fields. Data are plotted on a log2 scale to accommodate the large variations from case to case. In one case, CIC was found in 1 of 6 fields examined, the average value is <1 and the log value is <0. (B) The number of internalized CLL cells in the presence or absence of TME stimuli, IL-15/CpG, and CD40L; 20 cases of untreated CLL (left); ns (P = .322); 21 cases of treated CLL (right); ∗∗P = .011 (analyzed by the Wilcoxson test). (C-E) CIC identified in the BM aspirates from patients on BTKi therapy (n = 3). (F) Upon ibr exposure, CIC is not changed in NBCs (n = 5), increased in sensitive CLL (Ibr-S; n = 11) and increased in resistant CLL (Ibr-R; n = 6). Cells were treated ex vivo with 0.4-μM ibr for 5 hours. Also see images in supplemental Figure 5. (G) Time course of CIC in both Ibr-S (orange; n = 5) and Ibr-R cells (blue; n = 5). Also see images in supplemental Figure 7. ∗P = .02; ∗∗∗P = .001. Ibr-R, ibr-resistant cases; Ibr-S, ibr-sensitive cases; ns, not significant.

CIC is associated with prior therapies, increases with in vivo BTKi therapy and ex vivo ibr exposure. (A) Number of internalized cells were quantified for 43 CLL cases. Four to 6 fields were examined per sample. Each dot represents the average number of CIC per field per sample of 4 to 6 fields. Data are plotted on a log2 scale to accommodate the large variations from case to case. In one case, CIC was found in 1 of 6 fields examined, the average value is <1 and the log value is <0. (B) The number of internalized CLL cells in the presence or absence of TME stimuli, IL-15/CpG, and CD40L; 20 cases of untreated CLL (left); ns (P = .322); 21 cases of treated CLL (right); ∗∗P = .011 (analyzed by the Wilcoxson test). (C-E) CIC identified in the BM aspirates from patients on BTKi therapy (n = 3). (F) Upon ibr exposure, CIC is not changed in NBCs (n = 5), increased in sensitive CLL (Ibr-S; n = 11) and increased in resistant CLL (Ibr-R; n = 6). Cells were treated ex vivo with 0.4-μM ibr for 5 hours. Also see images in supplemental Figure 5. (G) Time course of CIC in both Ibr-S (orange; n = 5) and Ibr-R cells (blue; n = 5). Also see images in supplemental Figure 7. ∗P = .02; ∗∗∗P = .001. Ibr-R, ibr-resistant cases; Ibr-S, ibr-sensitive cases; ns, not significant.

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