Figure 4.
JNK1 inhibitors overcome TME-induced resistance mechanisms like the upregulation of antiapoptotic proteins. (A and B) Viability of IGHV unmutated (A, n = 11) or mutated (B, n = 12) CLL samples with or without stromal co-culture (M2-10B4 or CD40L secreting cells) after 24 h of SP600125 treatment (unpaired t test, *P < 0.05; **P < 0.01, ***P < 0.001). (C) Protein expression of p-JNK1 and total JNK1 in primary human CLL cells with or without stromal co-culture (M2-10B4 or CD40L secreting cells) and after 4 and 8 h of SP600125 treatment (CLL#29). (D) Relative expression of p-JNK1 in CLL samples either untreated, co-cultivated with M2-10B4 cells, or with CD40L secreting cells ± SP600125 treatment compared with β-actin and normalized to the control group (n = 4 CLLs) (unpaired t test, *P < 0.05). (E) Protein expression of p-c-JUN, c-JUN, p-BCL2, BCL2, p-MCL1, and MCL1 in primary human CLL cells with or without stromal co-culture (M2-10B4 or CD40L secreting cells) and after 8 h of SP600125 treatment (CLL#29). (F) Relative expression of p-MCL1, p-BCL2 and p-cJUN in CLL samples (n = 4) with or without stromal co-culture (M2-10B4 or CD40L secreting cells) and after 8 h of SP600125 treatment compared with β-actin and normalized to the control group. Statistical significance was calculated via a two-tailed unpaired t test (*P < 0.05; **P < 0.01, ***P < 0.001). Source data are available for this figure: SourceData F4.

JNK1 inhibitors overcome TME-induced resistance mechanisms like the upregulation of antiapoptotic proteins. (A and B) Viability of IGHV unmutated (A, n = 11) or mutated (B, n = 12) CLL samples with or without stromal co-culture (M2-10B4 or CD40L secreting cells) after 24 h of SP600125 treatment (unpaired t test, *P < 0.05; **P < 0.01, ***P < 0.001). (C) Protein expression of p-JNK1 and total JNK1 in primary human CLL cells with or without stromal co-culture (M2-10B4 or CD40L secreting cells) and after 4 and 8 h of SP600125 treatment (CLL#29). (D) Relative expression of p-JNK1 in CLL samples either untreated, co-cultivated with M2-10B4 cells, or with CD40L secreting cells ± SP600125 treatment compared with β-actin and normalized to the control group (n = 4 CLLs) (unpaired t test, *P < 0.05). (E) Protein expression of p-c-JUN, c-JUN, p-BCL2, BCL2, p-MCL1, and MCL1 in primary human CLL cells with or without stromal co-culture (M2-10B4 or CD40L secreting cells) and after 8 h of SP600125 treatment (CLL#29). (F) Relative expression of p-MCL1, p-BCL2 and p-cJUN in CLL samples (n = 4) with or without stromal co-culture (M2-10B4 or CD40L secreting cells) and after 8 h of SP600125 treatment compared with β-actin and normalized to the control group. Statistical significance was calculated via a two-tailed unpaired t test (*P < 0.05; **P < 0.01, ***P < 0.001). Source data are available for this figure: SourceData F4.

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