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Association details:
| Biomarker: | IKZF1 G151A overexpression |
|---|---|
| Cancer: | Diffuse Large B Cell Lymphoma |
| Drug: | avadomide (CC-122) (Cereblon modulator, Pleiotropic pathway modifier) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Deciphering the mechanisms of CC-122 resistance in DLBCL via a genome-wide CRISPR screen
Published date:
04/13/2021
Excerpt:
To determine the individual role of IKZF1, IKZF3, and ZFP91 in mediating the antitumor effect of CC-122 in DLBCL, we evaluated the growth inhibitory effect of CC-122 in DLBCL cell lines with stable overexpression of NanoLuc luciferase (as a negative control) or degradation-resistant mutated IKZF1, IKZF3, or ZFP91...overexpression of degradation-resistant mutations of IKZF1 or IKZF3 (IKZF1-G151A or IKZF3-G152A) conferred various degrees of significant resistance to CC-122 in all 4 tested cell lines...Therefore, it is likely that IKZF1 and IKZF3 can redundantly drive the survival of malignant B cells in DLBCL, providing an explanation for the complete rescue, with overexpression of either IKZF1-G151A or IKZF3-G152A.
DOI:
10.1182/bloodadvances.2020003431
