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Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/{beta}-Catenin Signaling in Chronic Lymphocytic Leukemia
In this study, we examined whether genetic silencing of ROR1 or inhibition of ROR1-signaling also could influence canonical Wnt signaling. To inhibit ROR1 signaling we used the humanized anti-ROR1 mAb cirmtuzumab, which is being evaluated in patients with CLL (Choi MY, et al, Cell Stem Cell, 22:951, 2018). Surprisingly, we found that CRISPR/Cas9 deletion of ROR1 in 293T cells also could enhance the capacity of Wnt3a to activate canonical Wnt-signaling, albeit to a lesser extent than CRISPR/Cas9 deletion of ROR2; conversely, re-introduction of ROR1 into ROR1-deleted 293T cells suppressed Wnt3a-induced activation of canonica...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, H., Zhang, S., Ghia, E. M., Choi, M. Y., Zhang, J., Chen, L., Widhopf II, G. F., Rassenti, L. Z., Kipps, T. J. Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases: Poster II Source Type: research
