Analysis of BIRC3 alterations in patients with chronic lymphocytic leukemia.

PATRICIA DOS SANTOS; DAVI TORRES; CAMILA GALVANO; CARMEN STANGANELLI; IRMA SLAVUTSKY; MARINA JIMÉNEZ; ROCÍO HASSAN

Mar del Plata

Congreso; LVIII Reunión Annual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

BIRC3 (Baculoviral IAP repeat containing 3) gene (11q22.2), located ~6Mb centromeric to the ATM (Ataxia telangiectasia mutated) locus (11q22.3), is a negative regulator of non-canonical NF-kB signaling pathway. We evaluated BIRC3 mutations and deletions in chronic lymphocytic leukemia (CLL) patients in order to have a better biologic characterization of the disease. Results were correlated with cytogenetics, FISH and IGVH (immunoglobulin heavy chain variable region) mutational status. A total of 80 patients were evaluated. Mutational status of exons 7, 8 and 10 was analyzed by PCR followed by bidirectional sequencing and compared with public databases. BIRC3/MALT1 Dual Color Dual Fusion Probe (Zytovision, Bioars) was used. The study was approved by the Institutional Ethics Committee. All individuals provided their informed consent. No BIRC3 mutations were observed. Three patients showed variants: rs17881197, rs7124969 and rs1055088, within exons 7, 8 and 10, respectively, all of them without clinical significance. The latter variant was associated to abnormal karyotype, TP53 deletion and unmutated (UM) IGHV. BIRC3 deletion was evaluated by FISH analysis in a selected group of 17 patients with ATM deletion. BIRC3 deletion was observed in 16/17 cases with the following distribution: 58% showed similar values in both genes, 25% had higher percentage of ATM deletion and 17% of cases showed increased frequency of BIRC3 deletion, suggesting clonal evolution. In addition, 77.8% of patients expressed UM-IGHV and 76.5% had abnormal karyotypes, 53.8% of them complex karyotypes. Interestingly, 64.3% of cases also showed TP53 deletion, associated to bad prognosis. To our knowledge, this is the first evaluation of BIRC3 alterations in CLL patients in our country. These results suggest very low frequency of BIRC3 mutations and highly variable size of deletions at 11q22 chromosomal region in our series. We identified a high-risk molecular group whose heterogeneity warrants further studied in the search for clinical correlations.