BCL6: somatic mutations and expression in early-stage chronic lymphocytic leukemia.
BCL6 somatic mutations affect normal and tumoral post germinal center B-lymphocytes. Our objective was to analyse expression, mutations and polymorphisms in the BCL6 gene and to correlate those variables with the clinical outcome in early-stage chronic lymphocytic leukemia (CLL). CLL samples were used for characterisation of the mutational status of BCL6/ immunoglobulin variable heavy chain (IGHV) genes, and expression of BCL6 was determined by real time PCR and immunoblot. Out of 68 cases, 29% show somatic mutations on BCL6 which occur exclusively in IGHV mutated cases. They are single nucleotide substitutions located mainly in two short mutational hot spots. CLL cells express different levels of BCL6 regardless of the mutational status, the number of mutations and polymorphisms. CLL cases expressing high levels of BCL6 have significantly shorter treatment-free interval. In conclusion, in early-stage patients with CLL, we found no correlation between expression and the mutations or polymorphism in BCL6, but high levels of BCL6 can discriminate patients with a worse prognosis.
Jantus Lewintre
Eloisa
E
Molecular Haematology Laboratory, Prince Felipe Research Centre, Valencia, Spain. jantus_elo@gva.es
Reinoso Martín
Cristina
C
García Ballesteros
Carlos
C
Pendas
Jehzabel
J
Benet Campos
Carmen
C
Mayans Ferrer
José Ramón
JR
García-Conde
Javier
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6; D016896:Treatment Outcome
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D051560:Proto-Oncogene Proteins c-bcl-6