Expression of ROR1, an oncoembryonic orphan-receptor found on chronic lymphocytic leukemia (CLL) B cells, may promote leukemia-cell activation and survival, thereby enhancing disease progression in patients with CLL, according to a study published in the journal Blood.1
ROR1 is a receptor for Wnt5a that may complex with TCL1, a co-activator of Akt that is capable of promoting development of CLL. In preclinical studies, researchers found that samples of CLL that expressed negligible ROR1 had lower expression and activation of Akt-signaling pathways compared with samples that expressed ROR1.
Although Wnt5 enhanced proliferation, chemotaxis, survival of CLL cells that expressed ROR1, investigators observed that Wnt5a did not have those effects in cells that did not express ROR1.
To evaluate the impact of ROR1 expression in patients with CLL, investigators identified samples from 797 patients with CLL for a training set. Samples were classified as ROR1-Hi or ROR1-Lo depending on their level of ROR1-surface-expression. The subgroups differed significantly in their median treatment-free survival.
Using 771 different samples for a validation set, researchers then determined that ROR1-Hi samples had a significantly shorter median treatment-free survival and overall survival compared with ROR1-Lo cases.
The findings suggest that patients with CLL who have high ROR1 expression may have worse treatment-free and overall survival. Further prospective evaluation is needed to confirm these results and determine if ROR1 is a useful biomarker in CLL.
1. Cui B, Ghia EM, Chen L, et al. High-level ROR1 associates with accelerated disease-progression in chronic lymphocytic leukemia. Blood. 2016 Nov 4. doi: 10.1182/blood-2016-04-712562. [Epub ahead of print]