ASSOCIATION OF GENETIC POLYMORPHISMS WITH DIFFERENTIAL CATALASE GENE
EXPRESSION IN PROGNOSTIC GROUPS OF CHRONIC LYMPHOCYTIC LEUKEMIA
PATIENTS
Marilisa Galasso1, Chiara Cavallini2, Francesca Maria Quaglia3, Ilaria Dando1, Ornella Lovato2, Mauro
Krampera3, Massimo Donadelli1, Maria Grazia Romanelli1 and Maria Teresa Scupoli1
(1)Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona,
Italy, (2)Research Center LURM, University of Verona, Verona, Italy, (3)Department of Medicine,
University of Verona, Verona, Italy
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course, with
some patients having indolent disease and others experiencing a more accelerated course,
treatment resistance and a dismal outcome. We have recently identified low catalase
expression as a major antioxidant element that identifies an indolent clinical behavior in CLL.
In contrast, high catalase expression is associated with a more aggressive disease course.
However, the precise molecular mechanisms controlling catalase expression and activity are
still poorly understood at both transcriptional and activity levels. The single nucleotide
polymorphism (SNP) -262 C/T in the promoter region of the catalase (CAT) gene has been
described to be associated with different levels of catalase in hepatocarcinoma and chronic
myelogenous leukemia cell lines as well as in erythrocytes.
The main objective of this study is to investigate regulatory mechanisms underlying
differential expression of catalase in CLL patients’ prognostic subgroups. Specifically, this
study aimed at characterizing the CAT SNP -262 C/T, which could be associated with
differential expression of catalase in CLL.
In leukemic cells isolated from 20 patients with CLL, we detected catalase expression levels
using quantitative reverse transcription polymerase chain reaction (RT-PCR). Genotyping of
the SNP -262 C/T (Id: rs1001179) in the promoter region of catalase was performed by PCR
restriction fragment length polymorphism PCR-RFLP. Then, PCR products were digested by
restriction endonuclease EcoR V and analyzed using gel electrophoresis. The CAT expression
levels were compared between different genotypes using Student t test.
We detected the homozygous CC genotype in 9/20 (45%) patients’ cells, the heterozygous CT
genotype in 9/20 (45%) patients, whilst 2/20 (10%) individuals were homozygous for the
mutant T-allele. The genotype frequencies in this population were in accordance with the
Hardy–Weinberg equilibrium. Then, we compared the catalase expression levels between the
groups of CLL samples exhibiting the CAT rs1001179 CC, and the CT/TT genotypes.
Interestingly, cases harboring the TT and CT genotypes exhibited a significantly higher
catalase expression compared with cells bearing the CC genotype.
This study establishes a significant association between the -262 C/T SNP and catalase
expression levels in CLL, thus indicating that CAT polymorphisms contribute to differential
catalase expression in CLL patients with divergent clinical outcome. Our data represent the
basis of future studies aimed at dissecting molecular mechanisms that regulate catalase
expression and activity in CLL, which could be of crucial relevance for the development of
therapies targeting redox pathways.
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