IGLV3-21 * 01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling

0301 basic medicine GENES Survival Überleben Immunoglobulin allele IGLV3-21 Immunoglobulins Prognose Receptors, Antigen, B-Cell Immunophenotyping 01 13Q14 Cohort Studies 03 medical and health sciences Immunoglobulin lambda-Chains Antigens, CD chronic lymphocytic leukemia (CLL) Autonomous BCR signaling LENGTH Humans Point Mutation Genetic Predisposition to Disease PROGNOSTIC INDEX info:eu-repo/classification/ddc/610 info:eu-repo/classification/ddc/570 B-Lymphocytes B cell antigen receptor (BCR); autonomous BCR signaling; chronic lymphocytic leukemia (CLL); immunoglobulin allele IGLV3-21*01; B-Lymphocytes; Cohort Studies; Complementarity Determining Regions; Genetic Predisposition to Disease; Humans; Immunoglobulin Heavy Chains; Immunoglobulin lambda-Chains; Leukemia, Lymphocytic, Chronic, B-Cell; Point Mutation; Receptors, Antigen, B-Cell immunoglobulin allele IGLV3-21*01 autonomous BCR signaling Immunogenetic phenomena Biological Sciences Prognosis B-Lymphozyten-Rezeptor Complementarity Determining Regions Leukemia, Lymphocytic, Chronic, B-Cell Chronic lymphocytic leukemia (CLL) 3. Good health B cell antigen receptor (BCR); autonomous BCR signaling; chronic lymphocytic leukemia (CLL); immunoglobulin allele IGLV3-21*01 DELETIONS Antigen CD38 Settore MED/15 - MALATTIE DEL SANGUE CD38 EXPRESSION IMMUNOGLOBULIN HEAVY Immunglobuline Chronisch-lymphatische Leukämie B cell antigen receptor (BCR) Immunoglobulin Heavy Chains
DOI: 10.1073/pnas.1913810117 Publication Date: 2020-02-11T21:55:37Z
ABSTRACT
Significance CLL is characterized by autonomous B cell receptor (BCR) signaling. CLL subsets are empirically defined by sequence similarities of the BCR heavy chain. However, in the unfavorable subset 2, an acquired mutation (termed R110) in the light chain stimulates autonomous BCR signaling. This study demonstrates that the oncogenic R110 mutation dictates the unfavorable prognosis and is not restricted to the conventional subset 2. Interestingly, carriers of a particular light-chain allele ( IGLV3-21 * 01 ) are predisposed to develop CLL because this allele enables autonomous BCR signaling by R110 as a single-point mutation. Monoclonal antibodies permit convenient screening for R110-expressing CLL, showing that it is the largest immunologically defined CLL subset and an example of functional rather than empirical CLL subclassification.
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