Effect of CYC202 on transcription and protein levels. Microarray analysis showing changes in expression of 52 selected genes in 5 B-CLL tumors following treatment with 5 μg/mL CYC202 for 4 hours. The cluster was visualized using TREEVIEW (http://www.microarrays.org/software.html). Columns represent individual B-CLL samples and rows correspond to genes. Color changes within a row indicate expression levels relative to the average of the same population: red = up-regulation, green = down-regulation. (B) Western blotting showing differential reduction in expression of antiapoptotic proteins, Mcl-1, Bcl-2, NFκB, HSP70, and TRAF 5, as well as proteins involved in repair (PCNA and XPA), in representative tumors of all 3 B-CLL subtypes following treatment with CYC202 for up to 24 hours. (C) Effect of CYC202 on RNA pol II in B-CLL. Western blotting with a phospho-specific antibody to serine 2 of the carboxy-terminal domain of RNA pol II showing down-regulation of RNA pol II phosphorylation after CYC202 treatment with 5 μg/mL of 2 ATM/TP53 wild-type B-CLL tumors (bottom panel). Western blotting showing down-regulation of total RNA pol II protein levels by 24 hours of CYC202 treatment in a representative ATM/TP53 wild-type B-CLL tumor (top panel).