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Review
. 2022 Oct 6;140(14):1583-1591.
doi: 10.1182/blood.2021014760.

ROR1: an orphan becomes apparent

Thomas J Kipps  1
Affiliations
Review

ROR1: an orphan becomes apparent

Thomas J Kipps. Blood. .

Abstract

Since its initial identification in 1992 as a possible class 1 cell-surface receptor without a known parent ligand, receptor tyrosine kinase-like orphan receptor 1 (ROR1) has stimulated research, which has made apparent its significance in embryonic development and cancer. Chronic lymphocytic leukemia (CLL) was the first malignancy found to have distinctive expression of ROR1, which can help distinguish leukemia cells from most noncancer cells. Aside from its potential utility as a diagnostic marker or target for therapy, ROR1 also factors in the pathophysiology of CLL. This review is a report of the studies that have elucidated the expression, biology, and evolving strategies for targeting ROR1 that hold promise for improving the therapy of patients with CLL or other ROR1-expressing malignancies.

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Conflict of interest statement

Conflict-of-interest disclosure: Zilovertamab was developed by T.J.K. and his laboratory and licensed by the University of California to Oncternal+ Therapeutics, Inc, and VelosBio, Inc, which provided stock and research funding.

Figures

Image 1
Graphical abstract
Figure 1.
Figure 1.
ROR1 signaling. The structure of ROR1 is provided with each of the various domains labeled in red font to the right or left of the ROR1 stick figure, marking the extracellular immunoglobulinlike domain, CRD, and Kringle domain and the intracellular tyrosine kinase–like domain, the serine/threonine-rich domains, and the proline-rich domain (PRD). The binding of Wnt5a to the CRD can trigger activation of ROR1 signaling with recruitment and activation of cytosolic accessory molecules in green rectangles via defined (solid arrows) or speculated (dashed arrows) signaling pathways, culminating in the expression of ERK1/2, NF-kB, and NRF2 target genes in the nucleus. Red rectangles delineate inactive or inhibitory signaling molecules. Small circles labeled P represent protein phosphorylation.
See this image and copyright information in PMC

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