Immunoglobulin Gene Sequence as an Inherited and Acquired Risk Factor for Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease characterized by the accumulation of CD5⁺ CD19⁺ malignant B cells. Autonomous ligand-independent B-cell signaling is a key process involved in the development of CLL pathogenesis. Together with other cytogenetic alterations, mutations in the immunoglobulin heavy chain variable (IGHV) gene act as a prognostic marker for CLL, with mutated CLL (M-CLL) being far more indolent than unmutated CLL (U-CLL). Recent studies highlight the role of a specific light chain mutation, namely, IGLV3-21^R110G, in the development and prognosis of CLL. Such a mutation increases the propensity of homotypic BCR-BCR interaction, leading to cell autonomous signaling. In this article, we review the current findings on immunoglobulin gene sequence mutations as a potential risk factor for developing CLL.