Analysis of VH gene sequences using two web-based immunogenetics resources gives different results, but the affinity maturation status of chronic lymphocytic leukaemia clones as assessed from either of the resulting data sets has no prognostic significance.
Some cellular and molecular features of chronic lymphocytic leukaemia (CLL) cells that are associated with prognosis may reflect the context within which their progenitors encountered antigen. It follows that the nature of antigen drive in CLL could influence the clinical course and we were prompted to assess the impact, if any, of affinity maturation (an antigen-driven process) on prognosis. Statistical models for assessing affinity maturation status are typically applied to V(H) gene sequence data analysed using a web-based resource like IMGT or VBASE. Since these resources differ with respect to some key relevant features, we evaluated a cohort of CLL cases by applying statistical models to V(H) data derived from both IMGT and VBASE. Important differences between the resulting data sets became apparent. These resulted from database variance and because IMGT and VBASE define complementarity-determining and framework regions (CDRs, FRs) in different ways. Thus, the numbers of mutations identified and their distribution between CDRs/FRs varied between the data sets for the majority of clones. Consequently, two different but overlapping sets of cases with evidence of affinity maturation were defined. Notwithstanding their differences, no significant associations of affinity maturation status with CD38 expression, p53 functional status or survival were identifiable in either data set.
Lane
B S
BS
Department of Haematology, Royal Liverpool University Hospital, Liverpool, UK.
Mensah
A A
AA
Lin
K
K
Pettitt
A R
AR
Sherrington
P D
PD
D036541:ADP-ribosyl Cyclase / Q000235:genetics; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D002999:Clone Cells; D019295:Computational Biology; D004252:DNA Mutational Analysis / Q000379:methods*; D030541:Databases, Genetic; D005260:Female; D006801:Humans; D007125:Immunogenetics / Q000706:statistics & numerical data*; D007128:Immunoglobulin Fragments / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008562:Membrane Glycoproteins; D009154:Mutation; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014584:User-Computer Interface
D015703:Antigens, CD; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains; D008562:Membrane Glycoproteins; D016159:Tumor Suppressor Protein p53; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1