Evolution of BCL-2/IgH hybrid gene RNA expression during treatment of T(14;18)-bearing follicular lymphomas.
Bcl-2, the gene over-expressed in follicular lymphomas (FL), is able to block chemotherapy-induced apoptosis. Consequently, we wondered whether bcl-2/IgH expression variations during treatment of FL could predict the outcome of patients with t(14;18)-bearing FL. For this purpose, we used a reverse transcription polymerase chain reaction (RT-PCR) assay to analyse 180 serial peripheral blood samples (PBS) during 34 treatment phases in 25 patients with t(14;18)-bearing FL. In all patients but two, bcl-2/IgH gene expression was demonstrated in pre-treatment samples. During 16 out of the 34 treatment phases (47%), bcl-2/IgH expression became negative: all but one were responders to chemotherapy. This conversion was transient in six cases. In 18 treatment phases, bcl2/IgH expression remained detectable: eight were clinically considered as treatment failures, while eight others achieved PR and two achieved CR. We observed a significant correlation between treatment response and RNA PCR results (P = 0.002). Three-year overall survival of patients with stable bcl2/IgH-negative conversion was 100% compared to 54% for the remaining patients (P = 0.069); 3-year freedom from progression was respectively 87.5% and 13% (P = 0.005). These results indicate a correlation between bcl-2/IgH expression variations and both clinical response and outcome. Whether this might predict disease outcome early remains to be confirmed.
Soubeyran
P
P
Department of Molecular Oncology, Institut Bergonié, Regional Cancer Center, Bordeaux, France.
Hostein
I
I
Debled
M
M
Eghbali
H
H
Soubeyran
I
I
Bonichon
F
F
Astier-Gin
T
T
Hoerni
B
B
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D016019:Survival Analysis; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm