Figure 1. BTK is a critical kinase for survival of ABC DLBCL cells.

A. RNA interference screen in lymphoma and multiple myeloma cell lines. An shRNA library targeting 442 kinases was screened in the indicated cell lines as described⁴. Shown is the selective toxicity of two BTK shRNAs after 3 weeks in culture. Bar values are mean +/− s.d. of four independent transductions. B. Selective toxicity of a BTK shRNA for ABC DLBCLs with wild type CARD11. DLBCL cell lines were infected with a retrovirus that expresses BTK shRNA #1 together with GFP. Shown is the fraction of GFP+ cells relative to the GFP+ fraction on day 2. C. BTK kinase activity is required for survival of ABC DLBCL cells. OCI-Ly10 cells were transduced with cDNAs encoding wild type or mutant BTK (kinase-dead allele or analog-sensitive kinase allele (ASKA)²⁹). Wild type but not kinase-dead BTK rescued cells with endogenous BTK knockdown. The ASKA isoform-specific kinase inhibitor 1-NM-PP1 (2 mM) killed cells bearing the BTK ASKA allele.