Figure 2.
JNK1 knockdown and JNK1 inhibition induces apoptosis in primary human CLL cells. (A) Knockdown efficiency in CLL patient samples using four different JNK1-siRNAs for 24 h (CLL#27; figure shows one out of four patient samples). (B) Viable CLL cells after 36 h of JNK1 knockdown using four different siRNAs (n = 4) in four different CLLs. Bar shows the mean viability for all four CLL patients (unpaired t test, *P < 0.05). (C) Correlation of JNK1 kd efficiency (A) with CLL cell viability (B). (D) Mechanism of action of the ATP-competitive JNK1 inhibitors SP600125 and CC-930 and the L-JNKi inhibitory peptide. (E) Relative amount of viable CLL cells treated with the three different JNK1 inhibitors at the indicated concentrations compared with DMSO control (n = 43 CLLs). (F) Relative amount of viable B cells from healthy donors after treatment with three JNK1 inhibitors at indicated concentrations compared to DMSO control (n = 5). (G) Response groups according to apoptosis induction after JNK1 inhibitor treatments with three different JNK1 inhibitors in 43 CLL patient samples. Sensitivity to one inhibitor was defined as relative apoptosis induction of >30% with the 2.5 µM inhibitor concentration (kinase inhibitors) and the 5 µM concentration (JNK1i) compared with control treatment. Responsive was defined as a CLL sample, which responded to all three inhibitors, intermediate responsive samples responded to one to two inhibitors and resistant samples did not respond to any inhibitor. (H–J) Quantification of relative viable CLL cells treated with three different JNK1 inhibitors for 24 h compared with controls, here showing all samples in the responsive group, which are sensitive to all three inhibitors (n = 21) (unpaired t test, *P < 0.05, **P < 0.01, ***P < 0.001). (K–M) Distribution of patient characteristics like sex, mutation status (IGHV mutated or unmutated), or prognosis according to karyotype and p53 status (complex karyotype, 11q-, 17p-, or p53 mutation) within the different response groups. Source data are available for this figure: SourceData F2.

JNK1 knockdown and JNK1 inhibition induces apoptosis in primary human CLL cells. (A) Knockdown efficiency in CLL patient samples using four different JNK1-siRNAs for 24 h (CLL#27; figure shows one out of four patient samples). (B) Viable CLL cells after 36 h of JNK1 knockdown using four different siRNAs (n = 4) in four different CLLs. Bar shows the mean viability for all four CLL patients (unpaired t test, *P < 0.05). (C) Correlation of JNK1 kd efficiency (A) with CLL cell viability (B). (D) Mechanism of action of the ATP-competitive JNK1 inhibitors SP600125 and CC-930 and the L-JNKi inhibitory peptide. (E) Relative amount of viable CLL cells treated with the three different JNK1 inhibitors at the indicated concentrations compared with DMSO control (n = 43 CLLs). (F) Relative amount of viable B cells from healthy donors after treatment with three JNK1 inhibitors at indicated concentrations compared to DMSO control (n = 5). (G) Response groups according to apoptosis induction after JNK1 inhibitor treatments with three different JNK1 inhibitors in 43 CLL patient samples. Sensitivity to one inhibitor was defined as relative apoptosis induction of >30% with the 2.5 µM inhibitor concentration (kinase inhibitors) and the 5 µM concentration (JNK1i) compared with control treatment. Responsive was defined as a CLL sample, which responded to all three inhibitors, intermediate responsive samples responded to one to two inhibitors and resistant samples did not respond to any inhibitor. (H–J) Quantification of relative viable CLL cells treated with three different JNK1 inhibitors for 24 h compared with controls, here showing all samples in the responsive group, which are sensitive to all three inhibitors (n = 21) (unpaired t test, *P < 0.05, **P < 0.01, ***P < 0.001). (K–M) Distribution of patient characteristics like sex, mutation status (IGHV mutated or unmutated), or prognosis according to karyotype and p53 status (complex karyotype, 11q-, 17p-, or p53 mutation) within the different response groups. Source data are available for this figure: SourceData F2.

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