ASSOCIATION OF –308TNF AND +252LTA SINGLE NUCLEOTIDE POLYMORPHISMS WITH HEMATOLOGICAL MALIGNANCIES IN CHILDREN FROM THE BASHKORTOSTAN REPUBLIC
Yakupova EV 1,* Krasavtceva TN2, Malyevsky OA2, Viktorova TV1
*Corresponding Author: Dr. Elvira V. Yakupova, Institute of Biochemistry and Genetics, Ufa Research Centre, Russian Academy of Science, Prospect Oktyabrya 69, Ufa 450054, Russia; Tel./Fax: +007-3472-356088; E-mail: ecolab_203@mail.ru
page: 9

INTRODUCTION

Hematological malignancies (HM) are the most common form of cancer in childhood. The incidence of AL in children is 3,7 per 100 000 in Bashkortostan Republic. Nowadays, then pediatric oncologists have become more successful at treating HM, cured rate in the developed countries nearly 80%, much of clinical research efforts have focused on stratifying patients into various risk groups based on known prognostic features (1). The prognostic factors now mostly include clinical and biological characteristics that are accessible at diagnosis. For example, the immunophenotype of the blasts is a highly significant prognostic aspect.  Advances in genetics have led to the discovery of new prognostic marks.

Tumor necrosis factor α (TNF) and Lymphotoxin α (LTA) are cytokines with pleotropic biological activities, which play an important role in the development and function of normal lymphoid tissue (2). It has also been shown that patients with malignant lymphomas have high circulating levels of TNF are associated with poor disease outcome (3). Several studies showed that excessive TNF production may influence the host status, including weight loss, cachexia, modification of the immune response, and anemia, therefore hampering the patient ability to tolerate his tumor and his treatment (4). Other experimental dates indicate that TNF may promote the growth certain lymphoid cells (5). Genes encode of these cytokines are located on chromosome 6p21, within a 7-kb DNA locus in the class III region of the major histocompatibility complex (6). In the promoter region of TNF gene has been described polymorphism -308G?A, which results in higher level of TNF expression (7). A polymorphic site +252A?G within the first intron of LTA gene also results in significantly higher LTA production (8).

The aim of this work was to test the -308TNF and +252LTA gene polymorphisms for association with HM in children from Bashkortostan Republic.

 




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