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

Abstract

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.

Genotyping chronic lymphocytic leukemia in China: East meets West

“…Despite the fact that the results were negative, these types of studies are important to perform in different ethnic groups. Similar previous studies have been conducted primarily in Europe, some of which found correlations between MDR1 genotype and clinical aspects of CLL such as response to therapy [7,8]. It is of value to reproduce such studies in ethnically diverse populations, to either confirm or refute such associations, and to elucidate the interplay of genetic and environmental factors.…”

“…MDR1 has found to be involved in resistance to chemotherapy in a wide range of malignant diseases, including leukemias [6]. It has also been implicated in causing both predisposition and resistance to treatment of many malignancies, including CLL [7,8]. This is interesting, since most drugs used to treat CLL are not MDR1 substrates.…”

Relationship Between Advanced Oxidation Protein Products, Advanced Glycation End Products, andS-Nitrosylated Proteins With Biological Risk and MDR-1 Polymorphisms in Patients Affected by B-Chronic Lymphocytic Leukemia

“…Nucleotide sequences were aligned to EMBL/GenBank and current databases (V-BASE sequence directory using We used this method for MDR1 evaluation (MDR1 gene RFLPs) because of its simplicity, specificity, reproducibility, and the cost kept, while several authors have reported the same method in their works (24)(25)(26)(27).…”

MDR-1 gene polymorphisms G2677T and C3435T in a case of Hodgkin’s variant of Richter’s syndrome

“…In a previous study, we noted a significant difference in the genotype distribution between B-CLL patients and the control group as well as significant differences in the genotype distribution between patients with high and low risk of progression, with a correlation with IgVH gene analysis and CD38 positivity (28). notably, since it is well known that the probability of transformation in RS is strongly associated with the CD38 polymorphism, the G allele is an independent risk factor for RS development (29).…”