Immunoglobulin lambda variable 3-21 (R110 variant) (IGLV3-21R110)

Immunoglobulin lambda variable 3-21 (IGLV3-21) with an arginine residue at position 110 (R110) is a specific molecular variant of the B-cell receptor (BCR) light chain that serves as a critical prognostic marker in Chronic Lymphocytic Leukemia (CLL). The presence of the R110 mutation, often resulting from a specific V-J rearrangement or somatic hypermutation, facilitates a unique homotypic BCR-BCR interaction that leads to autonomous, antigen-independent signaling (Minici et al., Nature Communications, 2017). This constitutive signaling drives the proliferation and survival of malignant B-cells, identifying a particularly aggressive clinical subset known as 'Subset #2' (Stamatopoulos et al., Blood, 2018). Patients with the IGLV3-21R110 variant typically experience poor outcomes and short time-to-first-treatment, regardless of the mutational status of their immunoglobulin heavy chain variable region (IGHV). While IGLV3-21R110 is not a direct target for traditional small molecule binding, it is a primary driver of the BCR pathway, making these patients candidates for targeted therapies such as Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors (Maity et al., Blood, 2020). Understanding this target is essential for risk stratification and selecting appropriate kinase-targeted interventions in B-cell malignancies.

Other names

IGLV3-21 subset #2IGLV3-21*01 with R110Immunoglobulin lambda variable 3-21 arginine 110CLL Subset #2 BCR

Inhibition of downstream Bruton's tyrosine kinase (BTK) signaling or B-cell lymphoma 2 (BCL-2) mediated anti-apoptotic pathways activated by the IGLV3-21R110-containing B-cell receptor.