Estudo do polimorfismo no códon 72 do gene TP53 na Leucemia Mielóide Crônica e associação com possível resposta ao tratamento com imatinibe
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2013-03-27
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Universidade Federal de Goiás
Resumo
The CML is a expansion clonal of cells progenitors hematopoietics and is associated to
an specific genetic lesion, known as the Philadelphia chromosome, product of the
reciprocal translocation t(9, 22)(q34, q11) that causes the oncogene BCR-ABL. The TP53
is a tumor suppressor gene located on the chromossome 17p13.1 coding for
phosphoprotein TP53. The polymorphism arises from the exchange of G for C at codon 72,
resulting the genotypes Arg/Arg, Arg/Pro and Pro/Pro. This study aims to determine the
allelic and genotypic frequencies of TP53 polymorphism at codon 72 in CML patients and
to correlate with the response to imatinib therapy. The work had the participation of 85
CML patients treated at the Clinic of Hematology, at Hospital das Clínicas – UFG in
Goiânia city, state of Goiás for the diagnosis and control of disease. To investigate the
allelic and genotypic frequencies, DNA samples were isolated from peripheral blood for
analysis of PCR reactions. For genotyping, forward and reverse primers were used for each
variant allelic. The study had the participation of 85 CML patients, which 69 were in
chronic phase, eight in accelerated phase and only one in blast crisis. The mean age was 51
years and eight months. The frequency of genotypes Pro/Pro, Arg/Pro and Arg/Arg was
11% (4/35) 43% (15/35) 46% (16/35) for patients resistant to imatinib treatment (group
case) and 16% (8/50) 62% (31/50) and 22% (11/30) for patients with response to imatinib
(control group), respectively. The population in this study is in Hardy-Weinberg
Equilibrium (x2 = 1, 12, P> 0, 05). Regarding age, gender, disease stage, and score Sokal
not observed an association of the disease with the response or resistance to treatment (P=
0,36; P = 0.82, P = 0.47 and P = 0.72), respectively. When we evaluated the genotypes
with respect to the Score Sokal (High x Intermediate/Low), it was observed that Pro/Pro
genotype was significantly lower in the high Sokal Score group than Intermediate/low (P =
0.017, OR = 8, 19). For criterion, age over 40 years old at diagnosis, by analyzing the
Fisher’s test, we found that patients carrying the Arg/Arg genotype are four times more
susceptible to produce any resistance to imatinib therapy. When we evaluated the variables
age, gender, disease phase, genotype and Sokal Score in logistic regression showed that
only the variable genotype was significant (P = 0.0159). Our results are not according to
the previous studies, in which suggest that the Pro/Pro genotype and the Pro allele can
check risk of developing disease or resistance to imatinib treatment. Our findings suggest
that patients carrying the Arg/Pro and Pro/Pro genotypes responded well to treatment and
that the Pro/Pro genotype represented an indicator for a good prognosis. Genotype Arg/Arg
represented a risk factor in genetic susceptibility in CML’s pathogenesis, contributing for a
worse outcome.
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SANTOS, Jeany Camelo. Estudo do polimorfismo no códon 72 do gene TP53 na Leucemia Mielóide Crônica e associação com possível resposta ao tratamento com imatinibe. 2013. 104 f. Dissertação (Mestrado em Genética e Biologia Molecular) - Universidade Federal de Goiás, Goiânia, 2013.