Categories of in vitro BCR response of 70 CLL short-term cultures and their associations with clinical parameters and tumor features
| Pattern of response to BCR stimulation . | Correlation with . |
|---|---|
| pERK1/2 activation at 2 h | High baseline pAKT (P = .06), short TTT (P = .05) |
| Code (n): 0 (12), 1 (2), 2 (5), 3 (3) | Lower in CLL with isolated -13q14 (P = .04) |
| pS473AKT activation at 2 h | TCL1 (P <.001), pan-pAKT target induction (P = .04), baseline pAKT (P = .05) |
| Strong: 36% (25 of 70) | sIgM and Rai stage (both P = .04), WBC and CD20 expression (both P = .02) |
| Mild: 41% (29 of 70) | Risk of not achieving a CR after F- and FCR-based frontline therapy (both P = .04) |
| None: 23% (16 of 70) | Inversely with maximum BCR-induced growth (P = .02) |
| TCL1 protein increase at 2 h | 2-hour pAKT response (P = .003), high baseline pAKT (P = .01) |
| Yes (n = 13), no (n = 53) | More likely in +12 (P = .02) and less likely in -11q22-23 karyotypes (P = .03) |
| Low peak WBC (P = .03), low no. of treatments (P = .02), long TTT (P < .001) | |
| Growth induction at 48 h | Major determinant: 2-hour pAKT response (P < .001) and maximum BCR-induced growth amplitude (P < .001) |
| Hyperresponsive: 28% (8 of 29) Dose-dependent: 34% (10 of 29) | Hyperresponsive group: higher in vitro baseline growth (P = .002), lower IL-4/CD40L-induced growth (P = .03), higher sIgM (P = .07), and baseline pAKT and CD25 expression (both P = .08) |
| No response: 38% (11 of 29) | Dose-dependent growth: high CD38 (P = .03) and WBC, short LDT and TTT (all P = .06), high Rai stage (P = .07) |
| Pattern of response to BCR stimulation . | Correlation with . |
|---|---|
| pERK1/2 activation at 2 h | High baseline pAKT (P = .06), short TTT (P = .05) |
| Code (n): 0 (12), 1 (2), 2 (5), 3 (3) | Lower in CLL with isolated -13q14 (P = .04) |
| pS473AKT activation at 2 h | TCL1 (P <.001), pan-pAKT target induction (P = .04), baseline pAKT (P = .05) |
| Strong: 36% (25 of 70) | sIgM and Rai stage (both P = .04), WBC and CD20 expression (both P = .02) |
| Mild: 41% (29 of 70) | Risk of not achieving a CR after F- and FCR-based frontline therapy (both P = .04) |
| None: 23% (16 of 70) | Inversely with maximum BCR-induced growth (P = .02) |
| TCL1 protein increase at 2 h | 2-hour pAKT response (P = .003), high baseline pAKT (P = .01) |
| Yes (n = 13), no (n = 53) | More likely in +12 (P = .02) and less likely in -11q22-23 karyotypes (P = .03) |
| Low peak WBC (P = .03), low no. of treatments (P = .02), long TTT (P < .001) | |
| Growth induction at 48 h | Major determinant: 2-hour pAKT response (P < .001) and maximum BCR-induced growth amplitude (P < .001) |
| Hyperresponsive: 28% (8 of 29) Dose-dependent: 34% (10 of 29) | Hyperresponsive group: higher in vitro baseline growth (P = .002), lower IL-4/CD40L-induced growth (P = .03), higher sIgM (P = .07), and baseline pAKT and CD25 expression (both P = .08) |
| No response: 38% (11 of 29) | Dose-dependent growth: high CD38 (P = .03) and WBC, short LDT and TTT (all P = .06), high Rai stage (P = .07) |