title: V(H)3-48 and V(H)3-53, as well as V(H)3-21, gene rearrangements define unique subgroups in CLL and are associated with biased lambda light chain restriction, homologous LCDR3 sequences and poor prognosis.
abstract: This study determined IgV(H) gene usage in 228 chronic lymphocytic leukaemia patients to investigate associations between gene usage and other biological or clinical characteristics. V(H)3-48 [N=8] and V(H)3-53 [N=4] gene rearrangements showed biased lambda light chain restriction and were predominantly found in female patients with short lymphocyte doubling time but without adverse prognosis cytogenetics. Overuse of V(L)3-21(Vlambda2-14) gene and highly homologous LCDR3 sequences were found in V(H)3-48 patients. V(H)3-21 gene usage [N=18, 7.9%] was associated with poor prognosis, overuse of V(L)3-21(Vlambda2-14) gene and highly homologous heavy- and light-chain CDR3 sequences, but was not associated with poor prognosis chromosomal aberrations.
authors.affiliation: Department of Haematology, Level C, Belfast City Hospital, Belfast, Northern Ireland, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Matthews
authors.forename: Mark A
authors.initials: MA
authors.lastname: Catherwood
authors.forename: T C M 'curly'
authors.initials: TC
authors.lastname: Morris
authors.forename: H Denis
authors.initials: HD
authors.lastname: Alexander
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains