D F Gluzman

National Academy of Sciences of Ukraine, Kievo, Kyiv City, Ukraine

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Publications (62)20.14 Total impact

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    ABSTRACT: 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.
    No preview · Article · Jun 2015 · Experimental oncology
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    ABSTRACT: Classical and up-to-date models of hematopoietic lineage determination are briefly reviewed with the focus on myeloid-based models challenging the existence of the common progenitor for T cells, B cells and NK cells. The analysis of immunophenotype of leukemic blast cells seems to be a promising approach for interpreting some controversies in the schemes of normal hematopoiesis. The lite-rature data as well as our own findings in the patients with various types of acute leukemias are in favor of the concept postulating that common myeloid-lymphoid progenitors giving rise to T and B cell branches retain the myeloid potential. The similarity of some immunophenotypic features of blast cells in pro-B acute lymphoblastic leukemia and acute monoblastic leukemia is consistent with monocyte origin postulated in the studies of normal hematopoiesis. Study of acute leukemias may be the challenging area of research allowing for new insight into the origin of hematopoietic cell lineages.
    No preview · Article · Mar 2015 · Experimental oncology
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    ABSTRACT: The issue of introduction of number of additions into actual scheme of blood formation is discussed. The long standing experience of laboratory diagnostic of oncologic hematological diseases in adults and children and the analysis of published data about normal blood formation are involved into consideration. The existence is surmised of common oligo-linear precursors for B-lymphocytes and monocytes, natural killer cells and monocytes and common cell-precursor of T-lymphocytes and dendrite cells as well. At the same time, the issue concerning the existence of human common cell-precursor of lymphization capable of differentiating into Band T-lymphocytes and natural killer cells is disputable.
    No preview · Article · Aug 2014 · Klinicheskaia laboratornaia diagnostika
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    Full-text · Dataset · Dec 2013
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    ABSTRACT: The state-of-the-art technologies of diagnosing acute leukemias based on the novel WHO classification have been developed. The major forms and cytological variants of hematoblastoses have been diagnosed precisely in 755 patients in Ukraine with one third of them suffering from acute leukemias (AL). The primers for detecting the transcripts of chimerical genes bcr/abl (t(9;22)(q34;q11)); mll/af4 (t(4;11) (q21;q23)); mll/ af9 (t(9;11)(p22;q23)) in reverse transcrip tase polymerase chain reaction (RT-PCR) have been desig ned. RT-PCR has been used for differential diagnostics in AL patients.
    No preview · Article · Feb 2013
  • D F Gluzman

    No preview · Article · Dec 2012 · Experimental oncology
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    ABSTRACT: Genetic mechanisms that result in the development and progression of B-cell chronic lymphocytic leukemia (B-CLL) are mainly unknown. We have analyzed gene expression patterns in Ukrainian B-CLL patients with the aim of identifying B-CLL involved / associated genes in order to shed light on the biology of this pathological entity. The samples of the peripheral blood and bone marrow of 44 Ukrainian B-CLL patients with no characteristics indicative of unfavorable course of the disease such as CD38 were analyzed morphologically and immunocytochemically according to the new WHO classification. Total RNA was isolated, and gene expression levels were determined by microarray method comparing with the sample from 17 healthy donors. We investigated interactions using the Ingenuity Pathway Analysis (IPA) software and found 1191 network eligible up-regulated genes and 3398 Functions/Pathways eligible up-regulated genes, 1225 network eligible down-regulated genes and 2657 Functions/Pathways eligible down-regulated genes. In B-CLL patients, gene networks around MYC, HNF1A and HNF4A, YWHAG, NF-κB1 and SP1 are identified as up-regulated; CEBPA, YWHAG, SATB1 and RB1 -- as down-regulated. G protein coupled receptor signaling, arachidonic acid and linoleic acid metabolisms, calcium signaling, metabolism of xenobiotics by cytochrome P450 are found out as significant up-regulated pathways. EIF2 and Cdc42 signaling, regulation of eIF4 and p70S6k signaling, protein ubiquitination pathway and oxidative phosphorylation are the most significant down-regulated pathways obtained in our study. The involvement of NF-κB gene network and upregulated levels of G protein coupled receptor signaling pathway, which has an important role in transcription of NF-κB, are important and need further examination.
    Full-text · Article · Mar 2012 · Experimental oncology
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    ABSTRACT: The complete medical consequences of the long-term exposure of population to ionizing radiation in post-Chernobyl period are still a controversial issue. The molecular biological analysis of malignant diseases of hematopoietic and lymphoid tissues in contaminated territories requires the precise diagnosis based on criteria of novel classifications. To analyze the relative gene expression of six apoptosis-related genes in different types of tumors of hematopoietic and lymphoid tissues in patients living in areas of Ukraine contaminated with radionuclides in post-Chernobyl period. The samples of the peripheral blood and bone marrow of 189 Ukrainian leukemia patients and 16 patients with reactive lymphocytosis were analyzed morphologically and immunocytochemically for precise delineation of the main forms and cytological variants of hematological malignancies according to new WHO classification. Expression of six apoptosis-related genes was analyzed in the individual samples of 9 different groups of malignant diseases of hematopoietic and lymphoid tissues and one group of patients with reactive lymphocytosis by quantitative RT-PCR. Expression of genes was assessed relative to that in control group of healthy donors. Up-regulation of six analyzed apoptosisrelated genes is observed in all groups of leukemia. In most groups of leukemia being analyzed, BCL-2 up-regulation level is superior to that of BAX. Prominent MYC up-regulation is observed in B-lymphoblastic leukemia/lymphoma, non-Hodgkin's lymphoma, and T-lymphoblastic leukemia/lymphoma groups. In myelodysplastic/myeloproliferative neoplasms, the striking up-regulation of Fas-1 and P38MAPK is evident. Practically all the groups of leukemia are characterized by stable high ratios of P53 up-regulation. In Ukrainian patients, up-regulation of six analyzed apoptosis-related genes is observed practically in all types of malignant diseases of hematopoietic and lymphoid tissues under study. Microarray-based analysis of these samples would be of great importance in terms of elucidating genomic interactions in leukemias and their possible association with ionizing radiation.
    No preview · Article · Jun 2011 · Experimental oncology
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    ABSTRACT: The data on the verified cases of mature B-cell neoplasms (chronic lymphocytic leukemia - CLL, B-prolymphocytic leukemia, non-Hodgkin's lymphoma in leukemization phase and multiple myeloma - MM; 146 cases in total) in the consecutive group of Ukrainian clean-up workers within 10-25 years after Chernobyl accident are summarized. B-cell neoplasms represent the most prevalent group among all diagnosed neoplasms of hematopoietic and lymphoid tissues in clean-up worker patients under study (49.4%). MM percentage in the patients of Chernobyl clean-up worker group turned out to be significantly higher than in the patients of the general populations studied at the same period. While the percentage of B-CLL is similar in clean-up worker patients and patients of general population, the trend towards younger age of patients with mature B-cell neoplasms in clean-up worker group is evident. The current concepts on the possible association between mature B-cell neoplasms (mainly B-CLL) and radiation exposure are briefly outlined. Only the precise diagnosis of hematopoietic malignancies combining with large-scale analytical epidemiological studies with careful dose assessment and long-term follow-up may represent the basis for resolving the question whether mature B-cell neoplasms may be radiogenic.
    Full-text · Article · Mar 2011 · Experimental oncology
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    ABSTRACT: The study included 1742 patients with acute myeloblastic leukaemias (AML) and acute lymphoblastic leukaemias (ALL), Kyiv city residents and patients from 20 regions of Ukraine. Bone marrow and blood smears were sent at diagnosis to Reference Center. The analysis was based on May-Grünvald-Giemza (MGG) stain and cytochemical reactions (MPO, acNSE, CAE, AP, PAS). Immunocytochemical techniques (APAAP, LSAB) and broad panel of monoclonal antibodies (MoAbs) against lineage specific and differentiation antigens of leukocytes were employed for immunophenotyping of leukemic blast cells directly in blood and bone marrow smears. Different types of AML were defined by the expression of the cell surface and cytoplasmic antigens. Immunocytochemical study was required especially in diagnosing of AML with minimal differentiation, acute megakaryoblastic leukaemia, acute erythroid leukaemia and acute leukaemias of ambiguous lineage. Acute lymphoblastic leukaemias was broadly classified into B-lineage and T-lineage ALL. According to the degree of B-lymphoid differentiation of the blast cells four subtypes of B-lineage ALL were established. T-lineage ALL observed in patients were also divided into four subtypes. Immunocytochemical examination was required to diagnose AL of ambiguous lineage with no clear evidence of lineage differentiation (acute undifferentiated leukaemia) or those with blasts that express markers of more than one lineage (mixed phenotype acute leukaemias).
    No preview · Article · Sep 2010 · Experimental oncology
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    ABSTRACT: To obtain polyclonal antibodies against recombinant proteins recognizing Bcr domain and fusion region of Bcr-Abl and analyze the patterns of intracellular distribution of Bcr and Bcr-Abl proteins in K562 cells of chronic myelogenous leukemia. The coding sequences of DH and PH domains of Bcr-Abl were cloned, and the recombinant proteins were expressed in E. coli. The rabbit polyclonal antibodies were produced and used for immunocytochemical study of Bcr and Bcr-Abl localization in K562 cells. The gene constructs containing sequences coding for DH and PH domains of Bcr-Abl have been obtained. The antibodies with relative specificity to corresponding recombinant proteins differ by the patterns of their intracellular reactivity with Bcr- and Bcr-Abl related structures. While Bcr protein is located predominantly perinuclearly, antibody against hybrid Bcr-Abl protein is reacted with the structures in cell periphery, namely on cell membranes. Antibodies against DH and PH domains of Bcr-Abl react with proteins located differently in chronic myelogenous leukemia cells. The difference in intracellular localization of Bcr and Bcr-Abl may be attributable to the different domains interacting with different multiprotein complexes.
    Full-text · Article · Jul 2010 · Experimental oncology
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Jan 2010 · ChemInform
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    ABSTRACT: The immunophenotypic profile of hematopoietic stem cells (HSC) and hematopoietic precursor cells as well as leukemic stem cells (LSC) has been extensively studied in several laboratories worldwide. The results of our studies suggest that the standard panel for classification of acute leukemias should be supplemented with several new markers allowing us to identify more precisely the different forms of the leukemias being of the closely related origin, for example AML M6b and AML M7. The common bipotent LSC in AML M7 of low grade and AML M6b may exist analogous to precursor cell common for megakaryocytopoiesis and erythropoiesis. We have also found the similarity between blast cells in pro-B-ALL [t (4;11), 11q23] and AML M5a [t (9;11), 11q23]. Such similarity of immunophenotype and cytogenetic abnormalities in blast cells in pro-B-ALL and AML M5a may be considered as hint explaining the cases of AML M5a as a recurrence of leukemia in children with originally diagnosed pro-B-ALL.
    Full-text · Article · Jul 2008 · Experimental oncology
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    N F Gamaleia · E D Shishko · D F Gluzman · L M Sklyarenko
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    ABSTRACT: To compare the sensitivity of normal and malignant human lymphocytes to 5-aminolevulinic acid (ALA) - mediated photodynamic damage. Blood lymphocytes isolated by Ficoll-sodium metrizoate density gradient from healthy donors (6) and hematologic patients (20) with different forms of lympholeukemia, and also transformed lymphocytes of human B-cell (Raji, Namalwa) and T-cell (MT-4, HUT-78) lines were investigated. Diagnoses of chronic lymphoproliferative disorders were made on the grounds of morphological, cytochemical and immunocytochemical studies of peripheral blood and bone marrow cells, with immunophenotype determination by monoclonal antibodies to differentiation antigens of T, B lymphocytes and NK cells and immunocytochemical ABC-AP method. Cells of leukemic B- and T-cell lines were cultured in standard RPMI-1640 medium. For photodynamic treatment, the cells were incubated with ALA and then irradiated by a helium-neon laser (wavelength of 633 nm). The number of dead cells was determined in 20 h with trypan blue dye exclusion test. The striking difference in responsiveness to ALA-mediated photodynamic treatment (ALA-PDT) between normal lymphocytes and cells isolated from lymphatic leukemia patients was established. A bulk of leukemic cells (mean for 10 patients with B-CLL - 62.06 -/+ 4.03%) were destroyed under the lowest ALA-PDT doses tested: 1 mM ALA, irradiation dose of 25 J/cm(2). However, it was virtually impossible to attain any appreciable damage of lymphocytes from healthy donors even with the highest treatment doses (5 mM ALA, 150 J/cm(2)). High sensitivity to ALA-PDT of malignant lymphocytes was confirmed in experiments with human T- and B-cell leukemic cell lines, and in these experiments, an anomalous reaction to the treatment of Raji cells was also detected. The mechanisms of the difference between normal and malignant lymphocytes are discussed in terms of altered heme-synthesis processes in malignant cells. 1) It is shown for the first time that blood lymphocytes from lymphatic leukemia patients are highly sensitive to the damage with ALA-PDT while lymphocytes of normal donors are practically not damaged. 2) Transformed lymphocytes of human T-cell lines are more sensitive than lymphocytes of B-cell lines. 3) Lymphocytes of the Raji line display anomalous dose-effect dependence with ALA-PDT. 4) It is proposed to evaluate the drastic difference in ALA-PDT responsiveness of normal and malignant lymphocytes as a possible simple and low-traumatic test for B-CLL screening among the elderly people.
    Full-text · Article · Apr 2008 · Experimental oncology
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    ABSTRACT: The structure of hematopoietic malignancies in post-Chernobyl period among pediatric patients in Kyiv city and 24 regions of Ukraine especially those born in 1986 and 1987 and the infants at the age below 1 year is reviewed taking into account the data of the Reference Laboratory obtained in 1993-2004 and based on the modern diagnostic technologies in accordance with FAB, WHO, EGIL, ICD-10 and ICD-O-2 classifications.
    Full-text · Article · Jul 2006 · Experimental oncology
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    ABSTRACT: The question as to whether the incidence of leukemias and malignant lymphomas among the Chernobyl clean-up workers increased in 20 years after the catastrophe is still a point of much controversy. Precise diagnosis of the main forms of hematopoietic malignancies according to FAB classification and new WHO classification and comparison of these data with that in the general population will be helpful in estimating the relative contribution of the radiation factor to the overall incidence of such pathologies. The data on 218 consecutive cases of malignant diseases of hematopoietic and lymphoid tissues in Chernobyl clean-up workers diagnosed in 1996-2005 are given in comparison with the data of 2697 consecutive patients of general population of the same age group. The morphology and cytochemistry of bone marrow and peripheral blood cells were studied. Immunocytochemical techniques (APAAP, LSAB-AP) and the broad panel of monoclonal antibodies to lineage specific and differentiation antigens of leukocytes were employed for immunophenotyping leukemic cells. Various types of oncohematological diseases developing 10-20 years after Chernobyl accident were registered in a group of clean-up workers under study including myelodysplastic syndromes (MDS), acute leukemias (ALL and AML), chronic myelogenous leukemia (CML) and other chronic myeloproliferative diseases, chronic lymphocytic leukemia (B-CLL) and other chronic lymphoproliferative diseases of B and T cell origin. MDS percentage among patients of clean-up workers group tended to exceed MDS percentage in the group of patients representing the general population examined at the same period (4.58 vs. 3.70%). Among 34 AML cases, leukemia was preceded by MDS in seven patients. The relative contribution of CML to the total number of clean-up workers with leukemia was higher than the corresponding percentage value in general population examined at the same period (9.17 vs. 6.59%). B-CLL was a predominant form of hematopoietic malignancies in clean-up workers under study (25.68%). Nevertheless, B-CLL percentage in patients of clean-up workers group did not differ significantly from that in the patients of general population. The multiple myeloma percentage (7.79%) in the group of patients belonging to clean-up workers in our study turned out to be twice as much as in the patients of general population (4.0%). The verified diagnosis of tumors of hematopoietic and lymphoid tissue according to modern classification (EGIL, WHO) could be the prerequisite for further molecular genetic and analytical epidemiology study of leukemias that may be related to Chernobyl NPP accident consequences.
    Full-text · Article · Apr 2006 · Experimental oncology
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    ABSTRACT: The question as to whether the incidence of leukemias and malignant lymphomas among the clean-up workers increased in 18 years after the catastrophe is still a point of much controversy. Precise diagnosis of the main forms of hematopoietic malignancies and comparison of these data with those in the general population will be helpful in estimating thr relative contribution of the radiation factor to the overall incidence of such pathologies. In all, 187 consecutive cases of malignant diseases of hematopoietic and lymphoid tissues in Chernobyl clean-up workers were analyzed in Ukrainian Reference Laboratory in 1996-2003. A total of 1942 consecutive patients of general population, mainly the residents of Kyiv city and district, diagnosed in References Laboratory at the same period comprised the group of comparison. The morphology and cytochemistry of bone marrow and peripheral blood cells were studied. Immunocytochemical techniques (PAP, APAAP, ABC) and the panel of monoclonal antibodies to differentiation antigens of leukocytes were employed for immunophenotyping leukemic cells. Various types of malignant disease of hematopoietic and lymphoid tissues were registered in Chernobyl clean-up workers under study including myelodysplastic syndromes (nine patients), acute lymphoblastic leukemia (eight) and acute myeloblastic leukemia (31), chromic myeloid leukemia (17), multiple myeloma (17) and other forms of chromic myeloproliferative and lymphoproliferative disease including B-cell chromic lymphocytic leukemia (49 patients). The verified diagnosis of tumors of hematopoietic malignancies according to modern classification (EGIL, WHO) could be the prerequisite for further analytical epidemiology study of leukemias that may be related to the Chernobyl accident.
    Full-text · Article · Feb 2005 · The Hematology Journal
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    ABSTRACT: In preparation for a possible large epidemiological study of radiation-related leukemia in Chernobyl clean-up workers of Ukraine, histologic evaluation of 62 cases of leukemia and related disorders was conducted by a panel of expert hematologists and hematopathologists from the United States, France, and Ukraine. All cases were randomly selected from a surrogate population of men in the general population of 6 regions of Ukraine who were between the ages of 20 and 60 years in 1986 and were reported to have developed leukemia, myelodysplasia, or multiple myeloma between the years 1987 and 1998. The hematologists and hematopathologists on the panel were in agreement with one another and with the previously reported diagnoses and classifications of about 90% of the cases of acute and chronic leukemia in the study. These results suggest that strong reliance can be placed on the clinical diagnoses of acute and chronic forms of leukemia and multiple myeloma that have occurred in Ukrainian Chernobyl clean-up workers providing that the diagnoses are supported by records of the patients having had adequate histologic bone marrow studies. The number of cases in this study with the diagnosis of myelodysplasia, however, was too small to draw firm conclusions.
    No preview · Article · Aug 2002 · International Journal of Hematology
  • D.F. Gluzman · I.V. Abramenko · V.M. Machilo
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    ABSTRACT: 102 Chernobyl clean-up workers (1986-1987) with suspected hematooncological diseases were examined for precise diagnosis of leukemias and lymphomas. MDS and different types of hematopoieitic malignancies have been diagnosed in 57 patients. 3 cases of unusual chronic lymphoproliferative disorder - large granular lymphocyte leukemia (LGL-L) have been diagnosed for the first time within the group under study. Detailed cytomorhological and immunophenotypical characteristics of blood and bone marrow cells in LGL-L patients have been presented with particular emphasis on the possible relationship between chronic lymphoproliferative disorders and exposure to ionizing radiation.
    No preview · Article · Mar 2000
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    ABSTRACT: During 1993-1997, 247 cases of childhood acute leukemia (AL) were analyzed among inhabitants of the city of Kiev and Kiev region, excluding the most contaminated areas belonging to the strict control zone. The criteria of an FAB classification supplemented by immunophenotyping data were applied. The AL pattern was shown to be quite typical except for several peculiar features characteristic of this regional group of patients, especially the absence of age peaks in children with acute myelogenous leukemias (AML), increased frequency of the T1 variant in T-cell acute lymphoblastic leukemia (ALL), and higher levels of M4 and M5 variants in AML. A typical variant of M5a-AML with minimal signs of differentiation was found.
    No preview · Article · Jul 1999 · Pediatric Hematology and Oncology