High Incidence of Bcl-2/IgH Rearrangement in Mexican Patients With Follicular Lymphoma and Its Relevance as a Marker for Minimal Residual Disease.

Abstract

Abstract Follicular lymphoma is frequently associated with the chromosomal rearrangement t(14;18)(q32;q21), which joints one of the JH segments of the heavy chains of immunoglobulins (IgH) gene in 14q32 with the Bcl-2 gene in 18q2, originating a chimeric protein. The frequency of this marker is unknown in the Mexican population. OBJECTIVE: To determine the incidence of the Bcl2-IgH rearrangement in Mexican patients with follicular lymphoma and its frequency as a marker of minimal residual disease after therapy. PATIENTS AND METHODS: 200 patients (102 male and 98 female) were evaluated; the analysis was made in peripheral blood samples (PB) in 64 cases (32%) or bone marrow (BM) in 136 (68%). Genomic DNA was obtained and the Bcl-2/IgH rearrangement was amplified by both PCR and nested PCR using primers for JH and exon-intron 3 region of Bcl-2 (MBR and MCR regions). The Bcl-2/IgH rearrangement was used as a marker to determine minimal residual disease (MDR) in 90 out of 200 patients in clinical remission, with a follow up ranging from 12 to 60 months; The incidence and tissue type analysis were compared using chi-square statistics. RESULTS AND DISCUSSION: We found a positive Bcl-2/IgH rearrangement in 80% of the Follicular NHL cases, with a breakage in the MBR region in 160 cases and in MCR in 10 cases, in the remaining 30 patients the Bcl-2/IgH was negative. We detected the Bcl-2/IgH rearrangement more frequently in the BM samples (86%) than in the PB (42%) (p<0.0001). Fifty of 90 initially Bcl-2/IgH positive patients converted to negative PCR, after treatment. It is also of interest that in this population the molecular response rates in BM were lower (18/50=36%) than in the PB (32/50=64%) (p<0.0001). In conclusion we found a high frequency of Bcl-2/IgH rearrangement in cases of follicular lymphoma in Mexican patients, highlighting the relevance of the molecular analysis at diagnosis and its use as a marker for molecular minimal residual disease.