Immunoglobulin lambda variable 3-21 (R110-mutated) B-cell receptor (IGLV3-21^R110 BCR)

The IGLV3-21^R110-mutated B-cell receptor is a specific variant of the B-cell receptor (BCR) complex found in a high-risk subset of Chronic Lymphocytic Leukemia (CLL) patients. This receptor is defined by the use of the IGLV3-21 gene and a characteristic somatic mutation that introduces an arginine residue at position 110 (R110) (Minici et al., Nature Communications, 2017). The presence of this mutation facilitates homotypic interactions between BCR molecules on the cell surface, leading to autonomous, antigen-independent signaling (Stamatopoulos et al., Blood, 2018). This continuous signaling drives the proliferation and survival of leukemic B-cells, contributing to an aggressive clinical phenotype regardless of the mutation status of the immunoglobulin heavy chain variable (IGHV) region. Consequently, IGLV3-21^R110 serves as a critical prognostic biomarker for poor outcomes and rapid disease progression (Nadeu et al., Blood, 2021). While no therapies currently target the R110 mutation directly, the signaling pathway it activates is effectively inhibited by small-molecule drugs such as Bruton's tyrosine kinase (BTK) inhibitors and PI3K inhibitors. Research into disrupting the specific homotypic binding interface of the IGLV3-21^R110 BCR represents a promising avenue for precision medicine in CLL.

Other names

IGLV3-21*01 BCRR110-mutated IGLV3-21Subset 2 CLL BCRIGLV3-21R110

Inhibition of the B-cell receptor signaling pathway downstream of the mutated receptor, specifically targeting Bruton's tyrosine kinase (BTK) or phosphoinositide 3-kinase (PI3K) to prevent autonomous cell proliferation.