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.
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.
Matthews
Christine
C
Department of Haematology, Level C, Belfast City Hospital, Belfast, Northern Ireland, UK.
Catherwood
Mark A
MA
Morris
T C M 'curly'
TC
Alexander
H Denis
HD
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
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains