PECULIARITIES OF POLYAMINE METABOLISM IN TRANSFORMED BLOOD CELLS OF PATIENTS WITH DIFFERENT FORMS OF LEUKEMIA
DOI:
https://doi.org/10.32471/oncology.2663-7928.t-23-4-2021-g.10067Keywords:
diagnostics, lymphoid tumors, polyamine synthesis enzymes, polyaminesAbstract
Summary. Polyamines (PA) — spermine, spermidine, and putrescine — play an important role in the processes of proliferation, growth, and differentiation in normal and malignant cells. In particular, various disorders of PA metabolism were found during the development of both experimental tumors and human cancer. At the same time, disorders of PA metabolism in human oncohematological diseases are extremely poorly studied. Aim: to evaluate the possibility of exploiting indicators of PA metabolism for the accurate diagnosis and course prediction of various forms of leukemia. Object and methods: the research was conducted on clinical material (peripheral blood mononuclear cells — PBMC) of 225 patients with various forms and cytological variants of leukemia (chronic B-lymphocytic leukemia (B-CLL) — 82; acute myeloid leukemia (AML M1-M5) — 65; acute B- and T-lymphocytic leukemia — 48; non-Hodgkin’s lymphoma — 30 patients) and healthy 10 donors. The isolation of PBMC lymphocytes was performed by centrifugation in a Ficoll-Urografin gradient. The high-pressure liquid chromatography, gel electrophoresis, Western blotting and statistical methods were used in the research. Results: significant variability in both arginase activity and its protein expression was found in the PBMC of patients with various forms of leukemia. Arginase activity/expression was the highest in patients with B-CLL; the lowest values were characteristic of the blast cell fraction of patients with B-аcute lymphoblastic leukemia. The arginase activity in the PBMC of patients with various forms of leukemia was significantly lower compared to that of healthy donor lymphocytes. It was found that the PBMC of patients with B-CLL is characterized by low levels of ornithine decarboxylase (ODC) expression, high level of spermine and low values of the spermidine/spermine (spermidine/spermine) ratio compared to patients with acute leukemia. It was shown that the levels of PA and spermidine/spermine ratio in the PBMC of different groups of patients with non-Hodgkin’s lymphoma differ significantly. The PBMC of patients with mantle cell lymphoma without signs of leukemia were characterized by low expression of ODC, putrescine and the spermidine/spermine ratio and high level of spermine. In the case of leukemic activity, the expression of ODC, putrescine, spermidine and spermidine/spermine ratio were 3–9 times higher. The highest levels of expression of ODC, putrescine and spermidine/spermine ratio were found in patients with T-lymphoblastic leukemia/lymphoma and B-prolymphocytic leukemia. Conclusions: activity/expression levels of arginase, ODC, spermine, spermidine and putrescine as well as spermidine/spermine ratio can be used as additional markers for the accurate diagnosis of various cytological variants of leukemia and the disease course prognosis.
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