CLINICAL SIGNIFICANCE OF THE TP53 MUTATION STATUS IN DIFFUSE LARGE B-CELL LYMPHOMA
Elena Nikolaevna VOROPAEVA1, Tatyana Ivanovna POSPELOVA2, Mikhail Ivanovich VOEVODA1, Vladimir Nikolaevich MAKSIMOV1
1Research Institutе of Internal and Preventive Medicine - Branch of Federal Research Center Institute of Cytology and Genetics of SB RAS
2State Medical University of Minzdrav of Russia
Keywords: ген ТР53, мутации, диффузная В-крупноклеточная лимфома, ритуксимаб, прогноз, таргетная терапия, gene TP53, mutations, diffuse large B-cell lymphoma, rituximab, prognosis, target therapy
Abstract
Objective: to reveal the clinical significance of the mutation status of the TP53 gene in the group of receiving rituximab therapy patients with diffuse large B-cell lymphoma (DLBCL) in Novosibirsk. Material and methods. A total of 74 patients with DLBCL, who have been hospitalized at the City Hematology Center in Novosibirsk for the period 2012-2015, were examined. All patients received therapy with rituximab. The nucleotide sequence of the coding region of the TP53 gene (exons 5-10) and adjacent regions of introns was analyzed by the Sanger direct capillary sequencing. Functional analysis of the revealed mutations was carried out. The results of the patients` therapy were evaluated. Results and discussion. For the first time, it has been revealed in the course of the study of Russian patients with DLBCL setting that TP53 mutation status is associated with the greater incidence of B-symptoms, splenomegaly, leukemia of the lymphoma, and poor prognostic groups according to the International Prognostic Index. A tendency toward a greater frequency of achieving complete clinical and hematologic remission during the therapy was revealed in the subgroup of patients with DLBCL having a canonical sequence of a gene or a mutation in TP53 with an unproven oncogenic potential. Patients with functionally significant TP53 mutations had a lower overall survival rates. Conclusion. For this reason, hopefully therapeutic approaches aimed at the inactivated pathway of TP53 can further improve clinical outcomes in DLBCL.
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