THE EXPRESSION OF THE MAIN AND ALTERNATIVE TRANSCRIPT (SORL1 Delta2) OF THE SORL1 GENE IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS AFFECTED BY THE CHORNOBYL ACCIDENT. / DOSLIDZhENNIa OSNOVNOGO I ALTERNATYVNOGO TRANSKRYPTU (SORL1 Delta2) GENA SORL1 U KhVORYKh NA KhRONIChNU LIMFOTsYTARNU LEAKEMIIu, POSTRAZhDALYKh VNASLIDOK ChORNOBYLSKA KATASTROFY.

OBJECTIVE: to study clinical-hematological data and expression of the main and alternative transcripts of SORL1 genein chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophe. METHODS: Analysis was performed in the main group of 34 CLL patients irradiated due to the Chornobyl NPP acci-dent (30 clean-up workers, and 4 evacuees) and in the control group of 27 non-irradiated CLL patients. Groups ofpatients were comparable by age, sex, stage of disease, mutational status of IGHV genes. Expression of the main andalternative transcripts of SORL1 gene was evaluated by Quantitative Real-time polymerase chain reaction (PCR). TheIGHV gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data wereanalyzed with the SPSS software package, version 20.0. RESULTS: Relative expression level of the main transcript of SORL1 gene was low (mean 1.71 ± 0.55, median 0.57),did not correlate with the IGHV gene mutational status, TP53 and SF3B1 mutations, stage of disease. The expressionof B transcript was not detected, F transcript was expressed at a very low level in 9 patients. The average relativeexpression level of SORL1-Δ2 transcript was 14.1 ± 6.04 (median 3.48; range 0.01-90.51). The expression of SORL1-Δ2transcript above the median was more frequent among patients on C stage (p = 0.001), and in patients with unmu-tated IGHV genes was associated with an extremely negative course of CLL (median of overall survival 9 months vs61 months at low expression). Relative expression levels of the main and alternative transcripts of SORL1 gene inpatients of the main and the control groups did not differ. CONCLUSIONS: Our preliminary data suggest that increased expression of SORL1-Δ2 transcript in CLL patients withunmutated IGHV genes can be considered as a negative prognostic marker.

EXPRESSION OF LIPOPROTEIN LIPASE AND c-MYC ONCOGENE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AFFECTED BY THE CHORNOBYL ACCIDENT. / EKSPRESIIa GENA LIPOPROTEÏNLIPAZY I ONKOGENA c-MYC U KhVORYKh NA KhRONIChNU LIMFOTsYTARNU LEIKEMIIu, IaKI POSTRAZhDALY VNASLIDOK AVARIÏ NA ChORNOBYL'S'KII AES.

OBJECTIVE: to determine the association between the expression of lipoprotein lipase (LPL) and c-MYC genes inperipheral blood cells of chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophedepending on the mutational status of IGHV genes. METHODS: Analysis was performed in the group of 69 CLL patients irradiated due to the Chornobyl NPP accident (58clean-up workers of 1986 year, 6 inhabitants of radionuclide contaminated areas, and 5 evacuees). The IGHV genemutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and c-MYCexpression was evaluated by Quantitative Real-time PCR. Data were analyzed with the SPSS software package, version 20.0. RESULTS: Relative LPL expression levels in CLL samples ranged from 0 to 1663.5 (mean 138.47 ± 30.69, median 26.1).A strong correlation between individual LPL expression levels and IGHV mutational status was found (r = 0.684;p < 0.0001). The average relative c-MYC expression level was 5.7 ± 0.87 (median 2.86; range 0-48.5). No association between c-MYC expression and IGHV mutational status was found. Among unmutated IGHV cases, a correlationbetween LPL and c-MYC gene expression levels was identified: r = 0.351; p = 0.013. CONCLUSIONS: Our data confirm the dominant concept that unmutated IGHV CLL cases are more sensitive to the actionof proliferative stimuli compared to mutated IGHV CLL cases. This is manifested by an increase in the expression ofa functionally significant LPL gene, is one for the strongest negative prognostic markers in CLL.

Distribution of rs2124594 genotypes in chronic lymphocytic leukemia patients depending on radiation anamnesis. / ROZPODIL GENOTYPIV ZA POLIMORFIZMOM rs2124594 U KhVORYKh NA KhRONIChNU LIMFOTsYTARNU LEY̆KEMIIu Z URAKhUVANNIaM RADIATsIY̆NOGO ANAMNEZU.

OBJECTIVE: to test the method of polymerase chain reaction with following fragments' length restriction to deter mine the rs2124594 polymorphism and to study its contribution in the development of chronic lymphocytic leukemia (CLL) in the post Chornobyl period. METHODS: Genotypes of rs2124594 were determined in 109 patients with CLL of B cell origin including 53 patients irradiated due to the Chornobyl NPP accident. Genotypes distribution among CLL patients was compared with healthy persons of European origin (the 1000 Genomes Project data set was used as a reference). RESULTS: Validity of the tested method was confirmed by direct sequencing. Associations between CLL risks and C allele (OR = 2.37; 95 % CI 1.50-3.73; р = 0.003), CLL risks and CT genotype (OR = 2.10; 95 % CI 1.38-3.21; р = 0.0012) were found. Distributions of rs2124594 genotypes in exposed and non exposed to ionizing radiation CLL patients did not differ. CONCLUSIONS: The association of single nucleotide polymorphisms across the 8q24 chromosome region (positioned at 127180736 and 127183014 near с MYC gene) with CLL risks was confirmed. Modified influence of ionizing radia tion on genetic susceptibility associated with rs2124594 was not found in this pilot study.

Myastenia and small doses of ionizing radiation: experience of successful use of rituximab for treatment of an irradiated with myasthenia gravis. / MIASTENIIa I MALI DOZY IONIZUIuChOÏ RADIATsIÏ: DOSVID USPIShNOGO ZASTOSUVANNIa RYTUKSYMABU DLIa LIKUVANNIa OPROMINENOGO Z MYASTHENIA GRAVIS.

A clinical case of the rituximab («Rituksim¼, «Mabthera¼) use to treat a man affected by the Chornobyl NPP acci dent with malignant resistant form of myasthenia gravis in conjunction with chronic mixed infection by Toxoplasma, Epstein Barr virus, Cytomegalovirus and Herpes simplex virus is described. In the dynamics of two year's observa tion the clinical efficacy of monoclonal antibodies was shown as the main symptoms stabilization and reducing doses of glucocorticoid and anticholinergic therapy. The positive effect was marked in the nearest and remote peri ods. Taking to account the efficacy, safety and good tolerability of rituximab, it is advisable to recommend treat ment for people exposed to ionizing radiation and developing myasthenia associated with chronic mixed infection by Toxoplasma, Epstein Barr, Cytomegalovirus and Herpes simplex virus.

[Informative value of the specialized registers in research of leukemia in Chernobyl accident liquidators in Ukraine].

The article considers the possibility of the use of current infrastructure of specialized population registers of Ukraine to study leukemia and other systemic blood diseases revealed in Chernobyl accident liquidators. Advantage and limitation of such registers in the use are discussed in the article. Ukrainian state register of people who suffered from Chernobyl accident and Ukrainian national cancer registers are the largest population registers in the country, which cover all the territory of Ukraine and contain information on each individual and may serve as source base for epidemiological studies. To solve issues on leukemia and other oncological diseases is recommended to use in complex data of specialized registers of Ukraine. It should be also taken into account necessity of using late registered cases and verifying registered diagnoses.

[The experience of FISH technique application for reconstruction of individual radiation doses in Chernobyl liquidators in the framework of Ukrainian-American project "Leukemia"].

The results of proper investigations received under the cytogenetic examination of 225 persons (control groups, Chernobyl liquidators exposed to different radiation doses, oncogematology patients) had been summarized and analyzed. The conclusion concerning possibilities and limitations of FISH technique usage for retrospective biodosimetry of human radiation exposure has been presented.

[Enterosorption and therapeutic plasmapheresis in the intensive therapy of patients with acute leukemia and of persons who were victims of the accident at the Chernobyl Atomic Electric Power Station]. / Enterosorbtsiia i lechebnyi plazmaferez v intensivnoi terapii bol'nykh ostrym leikozom i u lits, postradavshikh v rezul'tate avarii na ChAES.

The paper reports on the preliminary experience of treatment of those patients having been the victims to the reactor accident at the Chernobyl NPP as well as of those with acute and chronic leukoses, having received courses of modern cytostatic therapy. The patients were exposed to therapeutic plasmapheresis and enterosorption as part of a complex conventional treatment programme. The conclusion the authors have come to is as follows: enterosorption strikingly reduces manifestations of "cytostatic disease"; the use of plasmapheresis in those persons having been previously exposed to small dose chronic radiation, makes for improvement of clinical and laboratory values but further studies are warranted to determine indications for therapeutic plasmapheresis.

[The results of studies of the peripheral blood from children in Polesie District, Kiev Province and in the city of Kiev 4 years after the accident at the Chernobyl Atomic Electric Power Station]. / Rezul'taty issledovanii perifericheskoi krovi detei Polesskogo raiona Kievskoi oblasti i g. Kieva cherez chetyre goda posle avarii na Chernobyl'skoi AES.

The peripheral blood of 2200 children (age: from 2 to 16 years) inhabiting the Polessye District of Kiev Province and the city of Kiev 4 years after the Chernobyl atomic station accident was studied. An analysis of results revealed the presence of hematologic changes that may be interpreted as sequels of the effect of ionizing radiation on the body, while other changes may be considered as reactive and may in most cases accompany different somatic diseases of infectious-inflammatory character.