gene expression

Clinical and Prognostic Value of Molecular Markers of Diffuse Large B-Cell Lymphoma

REVIEWS , , , , , ,

SM Rastorguev1, DA Koroleva2, ES Boulygina1, SV Tsygankova1, NG Goncharov1, OS Naraikin1, NG Gabeeva2, EE Zvonkov2, AV Nedoluzhko1

1 National Research Center “Kurchatov Institute”, 1 Akademika Kurchatova sq., Moscow, Russian Federation, 123182

2 National Medical Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Artem Valer’evich Nedoluzhko, PhD in Biology, 1 Akademika Kurchatova sq., Moscow, Russian Federation, 123182; Tel.: +7(916)670-55-95; e-mail: nedoluzhko@gmail.com

For citation: Rastorguev SM, Koroleva DA, Bulygina ES, et al. Clinical and Prognostic Value of Molecular Markers of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019:12(1):95–100.

DOI: 10.21320/2500-2139-2019-12-1-95-100

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid tumor in adults which is associated with approximately 30–40 % of all non-Hodgkin’s lymphomas. Diagnostic criteria include diffuse growth of large anaplastic tumor cells, expression of В-cell markers, and a high proliferative index. Due to the development of molecular genetic technologies it became obvious that underlying cause of clinical diversity is a huge amount of genetic failures which determine epigenetic modification of gene expression, activation variability of certain signaling pathways, and immunological properties of tumor cells. The study and systemization of molecular markers present a significant trend in DLBCL diagnosis and treatment. This review discusses most important molecular markers and current view on their clinical value.

Keywords: lymphoma, DLBCL, B-cells, transcriptomics, gene expression, epigenomics, genomics.

Received: July 3, 2018

Accepted: December 10, 2018

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Cytogenetic and Molecular Genetic Prognostic Factors of Acute Lymphoblastic Leukemias

REVIEWS , , , ,

AV Misyurin

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

For correspondence: Andrei Vital’evich Misyurin, PhD, 24 Kashirskoe sh., Moscow, Russian Federation, 115478; e-mail: and@genetechnology.ru

For citation: Misyurin AV. Cytogenetic and Molecular Genetic Prognostic Factors of Acute Lymphoblastic Leukemias. Clinical oncohematology. 2017;10(3):317–23 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-317-323

ABSTRACT

This review presents characteristic and reproducible chromosome rearrangements in acute lymphoblastic leukemia (ALL), which can be detected with a standard cytogenetic research (G-bands staining) or by FISH. More subtle genetic changes, inaccessible to the observation of cytogeneticists, are detected with the help of modern methods of molecular biological diagnosis. The prognostic value of cytogenetic and molecular genetic markers of ALL is shown in this article. A minimal set of clinically relevant molecular markers is presented, which it is advisable to investigate with ALL.

Keywords: acute lymphoblastic leukemia, chromosomal aberration, chimeric oncogene, gene expression, gene mutation.

Received: December 3, 2016

Accepted: March 8, 2017

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Cytogenetic and Molecular Genetic Prognostic Factors of Acute Myeloid Leukemia

REVIEWS , , , ,

AV Misyurin

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

For correspondence: Andrei Vital’evich Misyurin, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: and@genetechnology.ru

For citation: Misyurin AV. Cytogenetic and Molecular Genetic Prognostic Factors of Acute Myeloid Leukemia. Clinical oncohematology. 2017;10(2):227–34 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-227-234

ABSTRACT

The review presents data on the diagnostic and prognostic value of cytogenetic and molecular genetic markers of acute myeloid leukemia (AML). It demonstrates that some cases, different types of AML subdivided on the basis of clinical and morphological characteristics earlier may be distinguished based on identification of specific genetic and chromosomal defects. However, some repeated chromosomal abnormalities may be detected in AML patients that may be assigned to different variants based in clinical and morphocytochemical signs. At present, it is widely accepted that changes in the karyotype are the key prognostic factors which are more important than criteria based on morphological and cytochemical signs. Therefore, the risk-adaptive therapy of AML should be chosen based on the cytogenetic test findings. The review contains a section discussing gene mutations known to date that may affect the AML treatment outcome.

Keywords: AML, chromosomal aberration, chimeric oncogene, gene expression, gene mutation.

Received: September 16, 2016

Accepted: January 3, 2017

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Correlation between Expression of RARa Transcription Factor and Genes of VEGFR3-Dependent Signaling System in Multiple Myeloma

EXPERIMENTAL STUDIES , ,

NN Kalitin, IV Buravtsova

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

For correspondence: Nikolai Nikolaevich Kalitin, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-17-69; e-mail: f.oskolov@mail.ru

For citation: Kalitin NN, Buravtsova IV. Correlation between Expression of RARa Transcription Factor and Genes of VEGFR3-Dependent Signaling System in Multiple Myeloma. Clinical oncohematology. 2015;8(1):31–5 (In Russ).

ABSTRACT

Background. All-trans retinoic acid (ATRA) is a natural metabolite of vitamin A, which can regulate the gene expression by means of interaction between different types of nuclear retinoic acid receptors (RARs). It has been demonstrated that it may lead to suppression of in vivo and in vitro tumor cell growth and can contribute to its survival. For example, in a number of studies, it has been demonstrated that one of RAR subtypes, RARa, modulates expression of a number of vascular endothelial growth factors (VEGFs), mainly VEGF-A. At the same time, the exact mechanisms regulating the RARa-mediated regulation of VEGF (especially VEGF-C and VEGF-D and their receptor VEGFR3) expression are still unclear.

Methods. Changes in expression of mRNAs of VEGF-C, VEGF-D genes and their receptor VEGFR3 in a group of 17 multiple myeloma patients before and after treatment were analyzed in the article. The obtained data were then compared with changes in gene expression of the RARa receptor.

Results. It has been found that overall levels of VEGF-C, VEGF-D and VEGFR3 gene expression were reduced in response to the therapy. Changes in expression of these genes correlated with the RARa expression.

Conclusions. The correlation between VEGF-C, VEGF-D and VEGFR3 expression and RARa expression could indicate a possible involvement of RARa- protein in regulation of VEGFR3-associated signaling system gene expression.

Scientific value. These results may describe a possible mechanism of VEGF-C, VEGF-D and VEGFR3 expression by the RARa transcription factor.

Keywords: multiple myeloma, gene expression, VEGFR3-dependent system, RARa.

Received: August 27, 2014

Accepted: October 20, 2014

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New molecular markers of CML progression

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , ,

V.A. Misyurin1,2, A.V. Misyurin1,2, L.A. Kesayeva1,2, Yu.P. Finashutina1,2, Ye.N. Misyurina2, I.N. Soldatova1,2, A.A. Krutov2, N.A. Lyzhko1,2, T.V. Akhlynina1,2, A.Ye. Lukina3, T.I. Kolosheynova3, N.V. Novitskaya1, Ye.G. Arshanskaya4, Ye.G. Ovsyannikova5, R.A. Golubenko6, V.A. Lapin7, T.I. Pospelova8, V.A. Tumakov9, and A.Yu. Baryshnikov1

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

2 GeneTechnology Medical Center, Moscow, Russian Federation

3 Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

4 Moscow Hematological City Center, S.P. Botkin City Clinical Hospital, Moscow, Russian Federation

5 Astrakhan State Medical Academy, Astrakhan, Russian Federation

6 Orel Regional Clinical Hospital, Orel, Russian Federation

7 Hematological Center, Yaroslavl City Clinical Hospital #1, Yaroslavl, Russian Federation

8 Novosibirsk State Medical University, Novosibirsk, Russian Federation

9 Ivanovo Regional Clinical Hospital #1, Ivanovo, Russian Federation

ABSTRACT

In the contrast to Ph’-negative chronic myeloproliferative disorders (cMPD), chronic myelogenous leukemia (CML) is prone to rather early transformation into the later stage disease, known as the acceleration phase (AP) and blast crisis (BC). Myeloproliferative disorders are termed myeloproliferative neoplasms in the WHO classification, 2008. Molecular mechanisms underlying CML progression are unclear and still being studied. Recently, it was shown that progression of some malignancies was associated with activation and hyperexpression of some genes from the cancer-testis (CT) family. In this study, we evaluated the gene expression profile of CT genes (GAGE1, NY-ESO-1, MAGEA1, SCP1, SEMG1, SPANXA1, SSX1 and PRAME) in the blood of patients with initially diagnosed cMPD, as well as in the blood and bone marrow of CML patients in CP, AP and BC. It was found that activation of these eight CT genes expression was strongly correlated with CML progression to AP and BP. These data suggest that at least some of CT genes can be involved in CML evolution towards the terminal phases. Expression of these genes can be used as an early molecular predictor of CML progression to AP and BC.

Keywords: cancer-testis genes, PRAME, gene expression, chronic myelogenous leukemia, chronic myeloproliferative diseases

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