[Certain biochemical features of leukocytes in blast crisis of chronic myelogenous leukemia]. / Nekotorye biokhimicheskie osobennosti leikotsitov pri blastnom krize khronicheskogo mieloleikoza.

The content of nuclear high mobility group (HMG) proteins, activities of ornithine decarboxylase (ODC), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and also glycosaminoglycan (GAG) content and composition were studied in leukocytes of patients with chronic myelogenous leukemia in the phase of blast crisis (BC CML). Myeloid and lymphoid cytochemical variants of BC CML differ by biochemical parameters. It is suggested, that the content of HMG-proteins, activities of ODC and PNP, and electrophoretic patterns of GAGs could be used in diagnostics of two main variants of BC CML.

[Thymidine kinase activity in leukocytes from patients with chronic myeloid leukemia at various periods in the disease]. / Aktivnost' timidinkinazy v leikotsitakh bol'nykh khronicheskim mieloleikozom v razlichnye periody zabolevaniia.

The level of thymidine kinase activity in the premature leukocytes of patients with chronic myeloleukemia during the stable phase was shown to serve as a measure of the disease development. Considerable variations in thymidine kinase activity in blast cells in myeloid and lymphoid blast crises demonstrated that analysis of the enzyme activity might be used in the biochemical diagnosis of blast crisis in chronic myeloleukemia simultaneously with the enzymes of purine metabolism--ADA and PNP. During cell differentiation, the activity of thymidine kinase was decreased and in the myeloid cells the enzymatic activity was much higher of that in lymphoid cells as shown by investigations using blast cells of patients with blast crisis in chronic myeloleukemia, cells K-562, thymocytes, spleen and peripheric blood lymphocytes. Isozyme thymidine kinase I was mainly responsible for the rate of enzymatic activity in premature leukocytes of patients with chronic myeloleukemia regardless of the disease stage.

[Distribution of alleles of DRB, DQB and DQA loci of major histocompatibility complex in healthy donors of Saint Peterburg]. / Osobennosti raspredeleniia allelei lokusov DRB, DQB i DQA glavnogo kompleksa gistosovmestimosti u zdorovykh donorov Sankt-Peterburga.

The distribution of alleles of DRB, DQB and DQA loci was investigated in 118 healthy donors from St. Petersburg. Said alleles were identified by the restriction fragment length polymorphism method using DRB, DQB and DQA probes after TaqI digestion and Southern blotting. The frequencies of said alleles were compared with those of a cohort of healthy donors living in Germany. A significantly higher frequency of DRB-17-2 was identified in the Russian donors, as compared with the German counterparts. Also, the Russian donors revealed a decrease in the frequency of DQB-1 (P = 0.01) and an increase in that of DQB-X allele (P = 0.05). An analysis of DRB, DQB and DQA locus a alleles adhesion in a sample of donors from St. Petersburg showed it to agree, in a large proportion of cases, with the literature data. A parallel study of immunological specificity of DR antigen was undertaken to compare the results of genetic and serologic typing; errors in DR specificity identification were found to have been made in 17.0%.

[The enzyme activity of purine nucleotide degradation and lymphoid cell subpopulations in children with the Diamond-Blackfan syndrome]. / Aktivnost' fermentov degradatsii purinovykh nukleotidov i subpopuliatsii limfoidnykh kletok u detei s sindromom Daiemonda--Blekféna.

Blood cells of 13 children with Diamond-Blackfan syndrome and their parents were examined for some immunological characteristics of lymphocytes and the activity of adenosine desaminase (ADA), purine nucleoside phosphorylase (PNP). Acute stage of the disease was characterized by high ADA activity of red blood cells and normal PNP activity in 75% of the patients. In remission these abnormalities persisted. High ADA activity was noted in 6 out of 14 parents of the children. Immunological investigation of the patients' lymphocytes revealed marked shifts in T-cellular immunity which may be responsible for impaired regulation of proliferation and differentiation of erythroid precursors registered in unbalance of purine degradation enzymes activity.

[Enzymatic markers in chronic myeloleukemia and their importance for identifying a blast crisis]. / Enzimaticheskie markery pri khronicheskom mieloleikoze i ikh znachenie dlia identifikatsii blastnogo kriza.

The paper summarizes data on the activity of adenosine deaminase and purine nucleoside phosphorylase which contribute to purine nucleotide degradation. The enzyme activity was studied in leukocytes of varying degree of differentiation obtained from 29 cases with chronic phase of chronic myeloid leukemia (CML), 19 patients with acute phase of the disease and from blasts of 32 cases with CML-associated blast crisis. In CML patients, lymphocytes of leukemic clones showed various levels of activity of the enzymes. Myeloid and lymphoid blast crises proved biochemically heterogeneous. The possibility to establish the nature of blast crisis in CML on the basis of profile of adenosine deaminase and purine nucleoside phosphorylase in blasts is discussed.

[Interrelation of degradation processes of purine nucleotides and their biosynthetic transformation in the blood cells of patients with acute leukemia]. / Vzaimosviaz' protsessov degradatsii purinovykh nukleotidov i ikh biosinteticheskikh prevrashchenii v kletkakh krovi bol'nykh ostrym leikozom.

It has been shown that the leukemic process shifts the balance of individual enzymatic steps of the purine nucleotide degradation and biosynthesis. In acute lymphoblastic leukosis (ALL) and acute myeloblastic leukosis (AML) the rate of purine degradation, as estimated by the ADA enzyme activity (ES 3.5.4.4.) and PNP (EC 2.4.2.1), exceeds considerably that of their enzymes AMP-DA (EC 3.5.4.6.) and IMP-DH (EC 1.2.1.14.) biosynthesis. The data obtained suggest the existence of differences in the enzymatic program of purine metabolism in the malignant transformation of hematopoietic tissue and in other tumours.

[Degradation of purines in leukocytes in acute nonlymphoblastic leukemias]. / O degradatsii purinov v leikotsitakh pri ostrykh nelimfoblastnykh leikozakh.

Activities of the enzymes, responsible for degradation of purine nucleotides in leukocytes, were distinctly dissimilar in M1, M2, M4 and M6 variants of acute non-lymphoblastic leukosis studied in 34 patients. Differentiation of leukemic cells was shown to be due to alterations in activity of adenosine deaminase and purine nucleoside phosphorylase, which were oppositely directed as compared with those observed in lymphoblasts under conditions of acute lymphoblast leukosis. Evaluation of activities of adenosine deaminase, purine nucleoside phosphorylase and 5'-nucleotidase is of importance for characteristics of individual variants of acute non-lymphoblastic leukosis and for elucidation of the state of leukemic clone differentiation, which may affect the efficiency of the therapeutic measures used.

[Adenosine deaminase, purine nucleoside phosphorylase and ecto-5'-nucleotidase--markers of acute leukemia variants]. / Adenozindezaminaza, purinnukleozidfosforilaza i ékto-5'-nukleotidaza--markery variantov ostrogo leikoza.

Estimation of enzymes participating in degradation of purine nucleotides--adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), ecto-5'-nucleotidase as well as the ratio of ADA/PNP in leukocytes was shown to be of importance in differential diagnosis of acute lymphoblast leukosis subforms and for identification of a nature of malignized leukocytes clone in acute undifferentiated leukosis. Importance of these analyses is determined by specific differences in distribution of the enzymatic activity in mononuclear cells in T-, non-T-, non-B-cell acute lymphoblast leukosis and acute myeloblast leukosis as well as due to similar level and ratios of these enzymatic activities in most cases of acute undifferentiated leukosis and in acute lymphoblast leukosis.

[Effect of purine nucleosides on human leukocytes in normal conditions and in leukemias]. / Vliianie purinovykh nukleozidov na leikotsity cheloveka v norme i pri leikozakh.

The degree of action of purine nucleosides (adenosine, deoxyadenosine (d-ado) and deoxyguanosine (d-gua] on peripheral blood leukocytes in leukemias has been shown to change, as estimated by their inhibition of the protein biosynthesis. The inhibitory effect of purines on lymphocytes of the CLL patients and on myeloid cells of patients is decreased as compared to the normal cells. On the contrary, blast cells in T-ALL and AML exhibit the increased sensitivity to d-gua and d-ado. The cytotoxicity of d-ado, as compared to that of other nucleosides, is markedly higher against both the normal and leukemic lymphoid and myeloid cells. The relationship between the differences in purine nucleoside action on the normal and leukemic cells and the peculiar features of the nucleotide metabolism in these cells is discussed.

[Enzymes of purine nucleotide catabolism in lymphocytes in normal states and in chronic lymphoid leukemia]. / Fermenty katabolicheskikh prevrashchenii purinovykh nukleotidov limfotsitov v norme i pri khronicheskom limfoleikoze.

Activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) as well as their ratio in chronic lymphocytic leukemia (CLL) were found to be several times lower as compared with normal cells and to depend upon the duration and severity of leukemic process. Ratio of ADA and PNP activities in CLL was inverted as compared with those of normal cells; 5'-nucleotidase activity varied within all the stages of the disease from zero values to supernormals. There was a correlation between beneficial effects of treatment of the CLL patients and an increase in ADA and PNP activities in their peripheral lymphocytes.

[Metabolism of nucleotides and RNA in leukocytes in chronic myeloleukosis]. / Obmen nukleotidov i RNK v leikotsitakh pri khronicheskom mieloleikoze.

Biosynthesis of purine and pyrimidine nucleotides was distinctly increased in leukocytes of patients with chronic myeloid leukosis, involving mainly the reutilization of preformed nitrogenous bases and nucleosides. An increase in the rate of 14C-orotate and 3H-uridine incorporation into the pyrimidine pool of myeloid leukosis cells correlated with stimulation of uridine kinase and orotidine monophosphate pyrophosphorylase, catalyzing biosynthesis of pyrimidine nucleotides in the reutilization pathway and de novo, respectively. The system of adenosine deaminase, providing the high rate of adenosine incorporation into the nucleotide pool, was apparently responsible mainly for the rate of reutilization synthesis of purine nucleotides in normal and leukemic leukocytes. Synthesis of RNA in leukocytes of patients with chronic myeloleukemia was increased mainly due to consumption of nucleotides formed via the reutilization pathway.

[Effect of adenosine on synthesis of pyrimidine nucleotides and RNA in normal lymphocytes and under conditions of chronic lymphoid leukosis]. / Vliianie adenozina na sintez pirimidinovykh nukleotidov i RNK v normal'nykh limfots takh i pri khronicheskom limfoleikoze.

Effect of exogenous adenosine on synthesis of pyrimidine nucleotides and RNA was studied in lymphocytes of the patients with leukemic form of chronic lymphoid leukosis. In presence of adenosine lymphocytes were incubated in mixtures containing the precursors--2,3-2(3)H-aspartic and 2-14C-orotic acids as well as 5-3H-uridine. Effect of adenosine on the activity of key enzymes of pyrimidine nucleotide synthesis (orotidine monophosphate pyrophosphorylase and uridine kinase) was studied. The enzymatic activity was estimated using radiochemical procedures in extracts of lymphocytes stored at -20 degrees after acetone drying. Adenosine similarly inhibited synthesis of pyrimidine nucleotides and RNA in normal and leukemic leukocytes. One of the mechanisms, by means of which the inhibitory effect of adenosine was realized, was related to the enzymatic activity of orotidine monophosphate pyrophosphorylase and uridine kinase.

[Coordination of the main and reutilization pathways of nucleotide biosynthesis in the lymphocytes in leukemia]. / Koordinatsiia osnovnogo i reutilizatsionnogo putei biosinteza nukleotidov v limfotsitakh pri leikoze.

Coordination of these two pathways of nucleotide synthesis in leukocytes under chronic lympholeukosis was studied using incorporation of 14C-orotic acid and 14C-uridine into uridine mono-, di- and triphosphates and also into RNA. Simultaneously, activity of the key enzymes, participating in metabolism of orotic acid and of uridine, was measured: OMP-pyrophosphorylase /EC 2.4.2.10, orotidine-5'-phosphate: purophosphate phosphorybosyl transferase/ and uridine kinase /EC 2.7.1.48, ATP: uridine-5'-phosphotransferase/. The reutilizational pathway of pyrimidine nucleotide synthesis was distinctly activated. At the same time there was only a slight increase in the main pathway of their synthesis in lymphocytes in leukemic form of cronic lympholeukosis. Activities of OMP-pyrophosphorylase and uridine kinase were increased by 30%. An impairment in the coordination of the rates of both pathways of pyrimidine nucleotide synthesis was related to inhibition of OMP-pyrophosphorylase caused by and increase in uridine nucleotide pool.

[Alteration of leukocyte AMP- and IMP-pyrophosphorylase stability in leukemia]. / Izmenenie termostabil'nosti AMF- i IMF-pirofosforilazy leikotsitov pri leikozakh.

Effect of thermic treatment and of pre-incubation with phosphoribosyl pyrophosphate on activity of AMP- and IMP-pyrophosphorylases were studied in leukocytes under chronic forms of limpho- and myeloleukoses. AMP-pyrophosphorylase from leukemia leukocytes was inactivated after heating up to 65 degrees, which, at the same time, as distinct from the enzyme of normal leukocytes, proved to be reversibly reduced after incubation of the heated cell extracts with phosphoribosyl pyrophosphate. IMP-pyrophosphorylase of leukocytes was activated at this temperature; the activation of the enzyme was 15--20% higher in leukemic leukocytes than in leukocytes of healthy donors. The data obtained demonstrate the increased thermostability of purine nucleotide pyrophosphorylase from leukemic leukocytes, which is apparently due to conformational peculiarities of the enzyme molecules.

[Phosphoribosyl pyrophosphate and its metabolic enzymes in the erythrocytes in certain forms of anemia]. / Fosforibozilpirofosfat i fermenty ego obmena v éritrotsitakh pri nekotorykh formakh anemii

Content of phosphoribosyl pyrophosphate and the activity of ribose phosphate pyrophosphokinase and AMP-pyrophosphorylase were studied in erythrocytes of healthy persons and of patients with various types of anemia. Deficiency of phosphoribosyl pyrophosphate and a decrease in the activity of enzymes studied were observed in erythrocytes under microspherocytic and hypoplastic anemia. The alterations correlated with impairments in energy metabolism. At the same time an activation of phosphoribosyl pyrophosphate enzymatic system and an increase of its content in erythrocytes did not depend on energy metabolism in Marchiafava--Micheli disease.