Fig. 1.

Inhibition of CHK1 results in BCL2-regulated cell death. a Western blot analysis showing the expression and activation status of CHK1 (pSer345) as well as MYC levels in ten different Burkitt lymphoma cells lines. b Dose response of Burkitt lymphoma cells lines to Chk1 inhibitor PF-477736. Survival was assessed using AnnexinV-staining and flow cytometry. c Burkitt lymphoma cells lines were treated for 48 h with the CHK1 inhibitor PF-477736 (CHK1i), either alone or in combination with the pan-caspase inhibitor QVD. Cells were processed for sub-G1 analysis using propidium iodide (PI) staining and flow cytometry. d Selected Burkitt lymphoma cell lines were transduced with a retrovirus enabling overexpression of anti-apoptotic BCL2 or an empty control vector. Cell death was assessed after 48 h of CHK1i treatment by sub-G1 analysis. e Nalm6, human B cell precursor acute lymphocytic leukemia (pre-B ALL) cells, were used to knock-out BAX and BAK using CRISPR/Cas9-based genome editing. The sub-G1 fraction of cells was determined by flow cytometry 48 h after CHK1i treatment. Bars represent means of n = 3/treatment ± S.E.M. *p < 0.05, **p < 0.01, ***p < 0.001 using unpaired Student´s t test