Background: Even 25 years after the Chernobyl catastrophe, the interpretation of the findings on leukemia risk among Chernobyl clean-up workers is still a point of much controversy. Precise diagnosis of the main types of hematopoietic malignancies according to FAB classification and new WHO classification may be helpful in estimating the relative contribution of the radiation factor to the overall incidence of such pathologies. Methods:The data on 295 consecutive cases of malignant tumors of hematopoietic and lymphoid tissues in Chernobyl clean-up workers diagnosed from 1996 to 2010 are given in comparison with the data of 2,697 consecutive patients other than clean-up workers of the same age group. For this study, a set of complex diagnostic techniques were used, including morphology, cytochemistry of bone marrow and peripheral blood cells, immunocytochemistry (APAAP, LSAB-AP) as well as the utilization of monoclonal antibodies to lineage specific and differentiation antigens of leukocytes.Results: All the main forms of tumors of hematopoietic and lymphoid tissues were diagnosed among clean-up workers under study in 10-25 years after the Chernobyl catastrophe including myelodysplastic syndromes (MDS), acute leukemias (ALL and AML), chronic myelogenous leukemia (CML) and other myeloproliferative neoplasms, chronic lymphocytic leukemia (B-CLL) and lymphoid neoplasms of B and T cell origin. Among 46 AML cases in clean-up workers, leukemia was preceded by MDS in seven patients. CML percentage tended to be higher in the group of patients representing clean-up workers (9.13% vs. 6.59%). B-CLL was a predominant form of hematopoietic malignancies in clean-up workers under study (26.10%). Nevertheless, the percentage of B-CLL in patients of clean-up workers group did not differ significantly from that in the non-exposed patients. The multiple myeloma percentage in our study was higher in the clean-up workers (6.46% vs. 4.00%). Conclusions:The verified diagnosis of tumors of hematopoietic and lymphoid tissues according to the up-to-date WHO classification could be prerequisite for further molecular genetics and analytical epidemiology study of leukemias that may be related to the Chernobyl catastrophe.

Summary. Response of chronic lymphocytic leukemia (CLL) patients to classical chemoimmunotherapy that remains the main strategy in treatment of this disease is strikingly variable. This issue requires the finding of biomarkers which could predict efficiency of drug administration and choose the best treatment option for each patient individually. The aim of this study was to find out association between cell surface receptors expression levels and CLL B cells sensitivity to chemotherapeutic drugs ex vivo. Materials and Methods: The study was performed on malignant B cells isolated from peripheral blood of primary CLL patients. Flow cytometry, qPCR, ex vivo drug sensitivity assay, and cell viability assay were used in this study. Results: The high CD5 expression level was linked to better bendamustine (BEN) and cyclophosphamide (CP) CLL B cells response in contrast to B cells with low CD5 expression. Sensitivity of CLL B cells to CP also could be predicted by high level of CD20 expression. Expression of CD38 and high levels of CD37 and CD40 showed CLL B cells resistance to BEN ex vivo. CLL B cells sensitivity to analyzed chemotherapeutic drugs was not dependent on CD22 expression status. The CD180 expression was detected in CLL B cells which were more susceptible to fludarabine and cyclophosphamide (FC) combinatory action. CLL B cells that coexpressed CD150 and CD180 on the cell surface were characterized by significantly decreased cell viability under fludarabine (FLU) exposure alone or FC in comparison with CD150-CD180- B cells. Cell surface expression level of CD150 was not associated with CLL B cells chemosensitivity. However, high mRNA expression level of mCD150 isoform in CLL B cells was linked to their FLU sensitivity and CP resistance, while high nCD150 mRNA expression level showed resistance to FLU. Simultaneous CD150 and CD180 ligation increased FLU resistance, but BEN susceptibility of CLL B cells. CD150 and CD180 alone or in combination are involved in upregulation of CD20 cell surface expression. Conclusion: Expression status of the CD5, CD20, CD37, CD38, CD40, CD150, and CD180 cell surface receptors could be used in prediction CLL B cells sensitivity to FLU, CP, BEN and FC ex vivo. Moreover, CD150 and CD180 receptors are involved in regulation of CLL B cells susceptibility to FLU and BEN. The CD150 and CD180 are positive regulators of CD20 expression that could make CD150+CD180+ CLL B cells more responsive to CD20-based immunotherapy.

Exposure to ionizing radiation is associated with increasing risk of various types of hematological malignancies. The results of major studies on association of leukemias and radiation exposure of large populations in Japan and in Ukraine are analyzed. The patterns of different types of leukemia in 295 Chernobyl clean-up workers diagnosed according to the criteria of up-to-date World Health Organization classification within 10–25 years following Chernobyl catastrophe are summarized. In fact, a broad spectrum of radiation-related hematological malignancies has been revealed both in Life Span Study in Japan and in study of Chernobyl clean-up workers in Ukraine. The importance of the precise diagnosis of tumors of hematopoietic and lymphoid tissues according to up-to-date classifications for elucidating the role of radiation as a causative factor of leukemias is emphasized. Such studies are of high importance since according to the recent findings, radiation-associated excess risks of several types of leukemias seem to persist throughout the follow-up period up to 55 years after the radiation exposure.

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To find out the cause of inhibition of the IL2-STAT5 signaling pathway in chronic lymphocytic leukemia (CLL) cells. Methods. CLL cells were isolated from peripheral blood, using gradient centrifugation on a ficoll-verografin mixture. Expression of the STAT1-6 genes at the mRNA level was analyzed, using the Oncomine database. Expression, phosphorylation status and cellular localization of the STAT5 protein were studied by fluorescence microscopy, using specific antibodies. Results. Unlike in B-cells of healthy donors, expression of the STAT5A protein was low in the patient CLL cells. As we have previously shown, the IL-2-STAT5 (JAK-STAT5) signaling pathway is inhibited in CLL cells. Now we demonstrated a low level of phosphorylation of the STAT5 protein, or a complete lack of phosphorylation in CLL cells. The STAT5A protein shows cytoplasmic localization, indicating the absence of complexes in the nucleus that activate/repress transcription of the STAT5-dependent genes. Conclusions. Inhibition of the IL-2-STAT5 pathway in CLL cells is caused by a lack of the STAT5 proteins phosphorylation and/or the absence of the active STAT5A transcription complexes in the nucleus of CLL cells.