MDR-1 polymorphisms (G2677T and C3435T) in B-chronic lymphocytic leukemia: an impact on susceptibility and prognosis.
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.
Penna
G
G
Division of Hematology, Policlinico G. Martino, University of Messina, Via Consolare Valeria, 98100, Messina, Italy.
Allegra
A
A
Alonci
A
A
Aguennouz
M
M
Garufi
A
A
Cannavò
A
A
Gerace
D
D
Alibrandi
A
A
Musolino
C
C
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D050438:Genes, Immunoglobulin Heavy Chain; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D007135:Immunoglobulin Variable Region