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

SIMPLE SUMMARY: Chronic lymphocytic leukemia (CLL) is the most prevalent among adult leukemias. Over the years, several research efforts discovered a lot of intricate details about the cause of the disease, its mechanism, and the prognostic factors that help to understand the progression and outcome of the disease. Mutations in the immunoglobulin gene sequences in B cells are the most important prognostic factor for CLL. The cells having no to very less mutations show aggressive disease, while those having more mutations are either fairly indolent or non-aggressive. In this review, we discussed the current gain of knowledge about these mutations and their effects in the overall disease pathology. ABSTRACT: 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.