TPMT genetic variations in populations of the Russian Federation.

Background: Polymorphisms that reduce the activity of thiopurine S-methyltransferase (TPMT) cause adverse reactions to conventional doses of thiopurines, routinely used for antileukemic and immunosuppressive treatment. There are more than 20 variant alleles of TPMT that cause decreased enzymatic activity. We studied the most common variant alleles of TPMT and their frequency distribution in a large cohort of multiracial residents in the Russian Federation and compared their frequencies in children with and without malignancy to determine whether TPMT gene abnormality is associated with hematologic malignancy.

[Umbilical blood is a source of hemopoietic stem cells for transplantation].

Aim: To develop and introduce into practice scientifically validated methods of collection, testing and storage of hemopoietic stem cells of umbilical blood (UB) for non-relative transplantations.

Material And Methods: UB and UB concentrate of 1004 mature newborns were studied with morphological, immunocytometric and cultural methods.

Results: The established reference values of the number of leukocytes and hemopoietic stem cells (HSC) are essential for examination whether UB is useable for production of the transplantation material.

Rapid genotyping of common deficient thiopurine S-methyltransferase alleles using the DNA-microchip technique.

Thiopurine drugs are metabolized, in part, by S-methylation catalyzed by thiopurine S-methyltransferase (TPMT). Patients with very low or undetectable TPMT activity are at high risk of severe, potentially fatal hematopoietic toxicity when they are treated with standard doses of thiopurines. As human TPMT activity is controlled by a common genetic polymorphism, it is an excellent candidate for the clinical application of pharmacogenetics.

[Abnormal methylation of p16/CDKN2A AND p14/ARF genes GpG Islands in non-small cell lung cancer and in acute lymphoblastic leukemia].

Multiplex methylation-sensitive PCR and methylation-specific PCR were employed in studying the methylation of CpG islands in the p16/CDKN2A and p14/ARF promoter and the first exon regions in non-small cell lung cancer (54 samples) and acute B-cell lymphoblastic leukemia (61 samples). Differences in methylation were detected between types of neoplasia as well as between CpG islands studied within the same types of tumors. High level of the p16/CDKN2A first exon CpC island methylation was revealed in non-small cell lung cancer (68%) and in acute B-cell lymphoblastic leukemia (55%) and the CpG island of p14/ARF first exon was nonmethylated in these types of tumors.

TNR/11q#1 trinucleotide (GCC)n repeat alleles and predisposition to acute and chronic leukemia.

TNR/11q#1 is a polymorphic trinucleotide (GCC)n repeat located within the minimal region of the 11q deletion in chronic lymphocytic leukemia (CLL). It was recently shown that certain alleles of this repeat are associated with a worse prognosis in CLL patients. To investigate the role of TNR/11q#1 variants as risk-modifying factors in leukemogenesis, we conducted a case-control study on 113 acute lymphotic leukemia (ALL) patients, 82 CLL patients and 146 healthy controls of Russian origin.

[Generation of oxygen free radicals by blood leukocytes of children with thrombocytopenic purpura. Regulatory role of products of platelet degranulation].

We studied the free radical status in children with thrombocytopenic purpura. The formation of reactive oxygen species was evaluated using luminol-dependent chemiluminescence. The studied group consisted of 25 children divided in subgroups by the form of the disease and glucocorticoid treatment.