REVIEWS

Role of c-MYC, BCL2, and BCL6 Expression in Pathogenesis of Diffuse Large B-Cell Lymphoma

REVIEWS , , , , ,

A.E. Misyurina1, V.A. Misyurin2, E.A. Baryakh1, A.M. Kovrigina1, S.K. Kravchenko1

1 Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: A.E. Misyurina, Graduate student 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(909)637-32-49; e-mail: anna.lukina1@gmail.com

For citation: Misyurina A.E., Misyurin V.A., Baryakh E.A., Kovrigina A.M., Kravchenko S.K. Role of c-MYC, BCL2, and BCL6 Expression in Pathogenesis of Diffuse Large B-Cell Lymphoma. Klin. Onkogematol. 2014; 7(4): 512–521 (In Russ.).

ABSTRACT

According to modern concepts based on results of examination of the gene expression profile, there are several subtypes of diffuse large B cell lymphoma (DLBCL): germinal center B cell-like (GCB) and activated B cell-like (ABC) lymphomas. Genes c-MYC, BCL6, and BCL2 are key regulators of B-cell germinal (follicular) differentiation. Genetic abnormalities with their participation are most common in molecular pathogenesis of DLBCL. A total level of activity as well as mechanisms that lead to overexpression each of these genes and production of corresponding proteins have an impact on a disease prognosis. We assume that quantitative assay of c-MYC, BCL6, and BCL2 gene expression, as well as proteins encoded by these genes, can allow to determine high risk DLBCL patients with great accuracy.

Keywords: diffuse large B cell lymphoma, molecular subtypes, risk groups, c-MYC, BCL6, BCL2.

Accepted: September 8, 2014

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Biology of Hematopoietic Stem Cell Niche

REVIEWS , , ,

N.Yu. Semenova, S.S. Bessmel’tsev, V.I. Rugal’

Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: S.S. Bessmel’tsev, DSci, Professor, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel: +7(812)717-67-80; e-mail: bsshem@hotmail.com

For citation: Semenova N.Yu., Bessmel’tsev S.S., Rugal’ V.I. Biology of Hematopoietic Stem Cell Niche. Klin. Onkogematol. 2014; 7(4): 501–510 (In Russ.).

ABSTRACT

The article presents up-to-date data on the role of bone marrow stromal niche in hematopoietic stem cells regulation (HSC). It describes stages of development of the hematopoietic niche concept. Characteristics of stromal cellular elements which form the niche are presented. Mechanisms of HSC regulation by the stromal niche are reported. The role of the niche in HSC leukemic transformation is discussed. It also presents data on structural changes in the niche in case of HSC development disorder.

Keywords: hematopoietic stem cell, bone marrow, hematopoietic stem cell niche, microenvironment.

Accepted: September 1, 2014

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Supplemental Blood Circulation System in Hematologic Malignancies

REVIEWS , ,

A.A. Vartanyan

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: A.A. Vartanyan, DSci, Senior scientific worker, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-10-65; e-mail: zhivotov57@mail.ru

For citation: Vartanyan A.A. Supplemental Blood Circulation System in Hematologic Malignancies. Klin. Onkogematol. 2014; 7(4): 491–500 (In Russ.).

ABSTRACT

Neoangiogenesis, i.e. formation of new blood microvessels on the basis of already existing vascular network, is a prerequisite for tumor growth. For years, neoangiogenesis has been considered the only way for delivering oxygen and nutrients to the tumor. However, over the last years, other mechanism of tumor vascularization has been studied. Formation of highly structured vascular channels from tumor cells in the absence of endothelial cells and fibroblasts surrounded by basal membrane, or vasculogenic mimicry (VM) is considered a supplemental blood supply system. VM was found in almost all types of tumors and its occurrence is strongly associated with poor prognosis. This review summarizes basic VM characteristics in solid tumors and hematological malignancies. It also discusses the clinical significance of the above mentioned phenomenon in diagnosing tumors and predicting their course.

Keywords: neoangiogenesis, vasculogenic mimicry, hematological malignancies.

Accepted: September 1, 2014

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Lymphomas in HIV-Infected Patients: Literature Review

REVIEWS , , , , , , ,

A.V. Pivnik1, N.V. Seregin2, Yu.G. Parkhomenko3,4, O.A. Tishkevich4, A.M. Kovrigina5, Е.B. Likunov6

1 N.N. Pletnev Moscow Clinical Research Center, Department of Health, Moscow, Russian Federation

2 Moscow Municipal Cancer Dispensary No. 3, Moscow, Russian Federation

3 Research Institute of Human Morphology, RAMS, Moscow, Russian Federation

4 Clinical Infectious Diseases Hospital No. 2, Department of Health, Moscow, Russian Federation

5 Hematology Research Center, RF MH, Moscow, Russian Federation

6 American Medical Center, Moscow, Russian Federation

Address correspondence to: pivnikav@gmail.com

For citation: Pivnik A.V., Seregin N.V., Parkhomenko Yu.G., Tishkevich O.A., Kovrigina A.M., Likunov E.B. Lymphomas in HIV-Infected Patients: Literature Review. Klin. onkogematol. 2014; 7(3): 264–77 (In Russ.).

ABSTRACT

This review presents data on incidence, pathogenesis, diagnosis, and treatment of lymphoid malignancies in HIV-infected patients. Articles published by Russian and foreign authors are being reviewed. The principle role of decreased CD4+ lymphocyte count in development of secondary diseases in HIV patients is emphasized. Data on the structure of death causes in HIV-infected patients published by Russian authors are presented. They demonstrate that lymphoma is the 5th most common death cause (of 6 leading death causes). Hodgkin’s lymphoma in HIV-infected patients is not discussed in the review, because its pathogenesis differs from that of aggressive lymphomas and requires a separate discussion.

Keywords: lymphomas in HIV-infected patients, HIV, AIDS, secondary disorders, death causes, pathogenesis, diagnosis, treatment.

Accepted: May 15, 2014

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B-Cell Receptor Signaling Pathway: Mechanisms and Inhibitors

REVIEWS , ,

E.A. Nikitin

Hematology Research Center, RF MH, Moscow, Russian Federation

For citation: Nikitin E.A. B-Cell Receptor Signaling Pathway: Mechanisms and Inhibitors. Klin. onkogematol. 2014; 7(3): 251–63 (In Russ.).

ABSTRACT

Differentiation and survival of normal B-lymphocytes critically depends on the B-cell receptor (BCR) signaling pathway. Lymphoid malignancies use different aspects of the BCR-signaling pathway to provide their proliferation and growth. They manifest themselves in different forms, such as the form of BCR particular antigenic specificity, or the form of activating or, to the contrary, inhibiting gene mutations encoding proteins involved in BCR-signaling. A number of small molecules inhibit different proteins of BCR-signaling cascade. In this review, we dwell on normal and defective BCR-signaling pathways, as well as on tyrosine kinase inhibitors that are being widely used in clinical trials and will likely change the management of lymphoid malignancies.

Keywords: В-cell lymphomas, B-cell receptor, kinase inhibitors.

Address correspondence to: еugene_nikitin@mail.ru

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Influence of chemotherapy on reproductive system: methods of protection and preservation of ovarian function

REVIEWS , , , ,

M.V. Volochayeva1, R.G. Shmakov1, and Ye.A. Demina2

1 V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, RF Ministry of Health, Moscow, Russian Federation

2 N.N. Blokhin Russian Cancer Research Centre, RAMS, Moscow, Russian Federation

ABSTRACT

The recent studies showed the great importance of discussing the issue of protection and preservation of the ovarian function in cancer patients. Nowadays, when new effective methods of treatment are available, many cancer patients wish to realize their reproductive function. In this review, we discuss the methods of ovarian protection such as pharmacological protection and IVF program including a cryopreservation and transplantation of ovarian tissue or cryopreservation of oocytes and embryos.

Keywords: fertility preservation, cancer, cryopreservation tissue, oocytes, embryos

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Autophagy: cell death or survival strategy?

REVIEWS , ,

O.V. Kovaleva, M.S. Shitova, and I.B. Zborovskaya

N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

The interaction between proliferation, differentiation, and programmed cell death is an integral part of the life-sustaining activity of multicellular organisms. The imbalance between these processes underlies the development of many human diseases. Understanding molecular mechanisms of these processes is important for identifying new diagnostic and therapeutic targets. During the last decade, the autophagy processed and its role in the cell life and death became a subject of great scientific interest. Autophagy represents a mechanism of intracellular substance utilization. Autophagy is a process that occurs in all cells under normal conditions. But under certain circumstances, this process can result in the cell death. Impaired autophagy significantly contributes into the development of some diseases (cancer, neurodegenerative and cardiovascular disorders etc.).

Keywords: apoptosis, autophagy, carcinogenesis

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Enzymes in oncohematology: relevant directions of experimental studies and prospects of clinical use

REVIEWS , , , , , ,

V.S. Pokrovskiy and H.M. Treshchalina

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation

ABSTRACT

Recently, the field of development of the novel enzyme-based drugs showed remarkable advances. In addition to L-asparaginase which have been already used in oncohematology for more than 30 years, the two new enzymes, L-arginine deiminase and ranpirnase, underwent the several phases of clinical trials. Anticancer activity in vivo at the preclinical stage was shown for a number of enzymes: L-methionine-gamma-lyase, L-lysine-alpha-oxydase, and binase. This review discusses the enzymes which possess anticancer activity and prospects for their use in oncohematology.

Keywords: anticancer enzymes, L-asparaginase, L-methionine gamma-lyase, L-lysine alpha-oxydase, L-arginine deiminase, L-phenylalanine ammonia-lyase, ranpirnase.

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Role of tyrosine-kinase inhibitor selectivity in development of adverse effects during treatment of chronic myeloid leukemia

REVIEWS , , ,

A.A. Zeifman1,2, E.Yu. Chelysheva3, A.G. Tukrina3, and G.G. Chilov1,2

1 N.D. Zelinsky Institute of Organic Chemistry, RAS, Moscow, Russian Federation

2 Fusion Pharma LLC, Moscow, Russian Federation

3 Hematology Research Center, RF MH, Moscow, Russian Federation

ABSTRACT

This review focuses on association between the selectivity of Bcr-Abl kinase inhibitors and the spectrum of their adverse effects during treatment of patients with chronic myeloid leukemia. The data on the structure and natural biochemical functions of the well-known adverse targets for inhibitors of Bcr-Abl kinases, including BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, and VEGFR1/2/3 are summarized, and the potential association between their off-target inhibition and adverse effects of tyrosine-kinase inhibitors is suggested.

Keywords: chronic myeloid leukemia, tyrosine-kinase inhibitors, selectivity, imatinib, nilotinib, dasatinib, ponatinib, PF-114, BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3.

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Past and present of radiotherapy in management of malignancies

REVIEWS , , ,

O.P. Trofimova, S.I. Tkachev, and T.V. Yuryeva

N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

The article describes the stages of emergence and development of radiotherapy in management of malignancies of various locations, covering the period from the discovery of X-rays to the use of 60Co artificial isotope and development of the linear electron accelerator. Currently, radiotherapy is required for 70 % of cancer patients at some stage of tumor treatment. Improvements in radiotherapy technologies and development of new irradiation techniques made possible to solve the main task of radiotherapy, i.e. tumor destruction with minimal radiation exposure to surrounding healthy tissues, at the time being. This paper describes the radiotherapy techniques and explains in detail the differences between conventional and conformal radiotherapy. Also, preparation of patients for radiotherapy and the features of various conformal radiotherapy technologies are included.

Keywords: irradiation, radiotherapy, preparation for radiotherapy, linear electron accelerator.

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