MDR-1 polymorphisms (G2677T and C3435T) in B-chronic lymphocytic leukemia: an impact on susceptibility and prognosis

• Published in: Medical oncology (Northwood, London, England) Vol. 28; no. 4; pp. 1549 - 1554
• Main Authors: Penna, G., Allegra, A., Alonci, A., Aguennouz, M., Garufi, A., Cannavò, A., Gerace, D., Alibrandi, A., Musolino, C.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2011; Springer Nature B.V
• Subjects: Aged; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Biomarkers, Tumor - genetics; CD38 antigen; Cell Separation; Female; Flow Cytometry; Genes, Immunoglobulin Heavy Chain; Genetic Predisposition to Disease; Genotype; Hematology; Humans; Immunoglobulin Variable Region - genetics; Internal Medicine; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Male; Medicine; Medicine & Public Health; Neoplasm Staging; Oncology; Original Paper; Pathology; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prognosis; B-chronic lymphocytic leukemia; MDR1; Gene polymorphism; Prognostic marker
• ISSN: 1357-0560; 1559-131X; 1559-131X
• DOI: 10.1007/s12032-010-9561-9

Patients with B-chronic lymphocytic leukemia present diverse clinical features, genetic abnormalities, variable response to treatment, and heterogeneous prognosis. Novel biological markers such as IgVH mutation, CD38, and ZAP-70 expression have shown to offer important prognostic information. An altered expression of the multidrug resistance 1 may represent an additional prognostic marker. Aim of our study was to evaluate two MDR-1 gene polymorphisms: G2677T polymorphism in exon 21 and C3435T polymorphism in exon 26, to evidence if polymorphisms influence the risk of development of B-CLL and whether genomic polymorphisms provide prognostic information on the clinical progression of the disease. A total of 125 patients with B-CLL and 125 healthy subjects were enrolled in this study. The mutant homozygous 2677 TT genotype was found to be associated with the occurrence of B-CLL and higher T allele frequency in patients with B-CLL when compared with controls was observed ( P  = 0.009). When comparing the prognostic patients’ characteristics, patients with 2677 GT genotype were statistically linked to the unmutated IgVH genes ( r  = 0.209, P  = 0.01). Moreover, the same genotype was correlated with lymphocyte number ( r  = 0.269, P  = 0.02). Finally for the 2677GT polymorphism, the heterozygous status was associated with higher hemoglobin levels ( r  = 0.247, P  = 0.005). As far the C3435T MDR1 polymorphism, we were not able to identify any significant correlation with IgVH gene status or other variables. In conclusion, MDR1 gene polymorphism could be a factor predisposing to LLC. Moreover, our findings support the possibility of considering these genomic polymorphisms as prognostic markers in patients with B-CLL.