Page 114 - Haematologica May 2022
P. 114
J. Gao et al.
A
B
C
D
Figure 1. Mantle cell lymphoma and other B-cell lymphoma cell lines and primary samples are exquisitely sensitive to CDK12 inhibition with THZ531, regardless of genetic background and drug resistance status. (A) Bar plot of log10 of 50% inhibitory concentration (IC50) of B-cell lymphoma cell lines treated with THZ531 for 72 h. (B) Correlation of MCL-1 (left) or phosphor-4EBP1 protein level (right) with THZ531 IC50 in B-cell lymphoma cell lines. (C) Image-based cell-viability assays of pri- mary mantle cell lymphoma samples; 3x106 cells were seeded in a 384-well plate with extracellular matrix and lymphoma stromal cells. THZ531 at five serial diluted concentrations was added to the medium, and the plate was continuously imaged every 30 min for 144 h. All images were analyzed using a digital imaging analysis algorithm to detect cell viability based on membrane motion, and changes in viability were quantified by area under the curve (AUC). (D) Correlation of MCL-1 (left), ATM (middle) and ATR (right) gene expression (log2TPM) with CDK12 gene expression (log2TPM) in primary patients’ samples. Data shown in (A) are representative of at least three independent experiments. TPM: transcripts per kilobase million.
1122
haematologica | 2022; 107(5)
