Publications by authors named "Anait L Melikyan"

4 Publications

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Low V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional or Gene Mutations.

Genes (Basel) 2021 Apr 12;12(4). Epub 2021 Apr 12.

National Research Center for Hematology, Novy Zykovski lane 4a, 125167 Moscow, Russia.

(Janus kinase 2) V617F, (Calreticulin) exon 9, and (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefore, after the emergence of one type of mutation, other types should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Our study includes DNA samples from 1958 patients with clinical evidence of MPN, admitted to the National Research Center for Hematology for genetic analysis between 2016 and 2019. In 315 of 1402 cases (22.6%), mutations were detected. In 23 of these 315 cases (7.3%), the JAK2 V617F mutation was found in addition to the mutation. In 16 from 24 (69.6%) cases, with combined and mutations, V617F allele burden was lower than 1%. A combination of V617F with W515L/K was also observed in 1 out of 1348 cases, only. allele burden in this case was also lower than 1%. Additional mutations may coexist over the low background of JAK2 V617F allele. Therefore, in cases of detecting MPNs with a low allelic load V617F, it may be advisable to search for other molecular markers, primarily mutations in exon 9 of . The load of the combined mutations measured at different time points may indicate that, at least in some cases, these mutations could be represented by different clones of malignant cells.
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http://dx.doi.org/10.3390/genes12040559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069892PMC
April 2021

Clinical Characteristics of Cerebrovascular Pathology with Patients Suffering from Ph-Negative Myeloproliferative Disease.

Cerebrovasc Dis Extra 2016 7;6(3):66-70. Epub 2016 Sep 7.

Angioneurology, Research Center of Neurology, Moscow, Russia.

Background: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD) and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph) myeloproliferative disorders (MPD) including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PM).

Materials And Methods: The study included 167 patients: 102 patients with Ph-MPD and the control group comprising 65 patients with CVD. According to MPD subtype, the patients were divided into three groups: patients with ET (37%, n = 38, male/female 7/31, age 52 ± 7 years), those with PV (40%, n = 41, male/female 20/21, age 50 ± 6 years) and those with PM (23%, n = 23, male/female 5/18, age 54 ± 4 years).

Results: In 79% (n = 81) of cases in the study group (with Ph-MPD), patients had chronic CVD, with the most frequently identified symptoms being asthenia (92%) and headache (72%). Headache in Ph-MPD patients was more frequently (86%) associated with PM, while in patients with PV and ET it was equally distributed (70%). Neurological symptoms in 53% of cases were associated with focal changes of the brain on MRI localized in the subcortical area of the frontal and parietal lobes. Twenty-one (21%) patients suffered an acute cerebrovascular accident, 8 of them had thrombotic occlusion of one of the internal carotid arteries leading to hemispheric infarcts. Endothelial function (as measured by flow-dependent dilation of the brachial artery) was severely impaired in all study groups (median 5% with normal cut-off at 10%), the lowest degree of vasodilator activity being specific for patients with a history of stroke (p = 0.011).

Conclusion: Patients suffering from MPD had asymptomatic focal changes in the brain in the absence of concomitant vascular disease (hypertension, atherosclerotic vascular disease, heart rhythm disorders) in 50% of cases. MPD, while remaining un- or underdiagnosed, presents a major concern in the cerebrovascular setting. A large number of thrombotic strokes occurring in patients with ET underline the necessity of early diagnostics and preventive therapy in these patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040904PMC
http://dx.doi.org/10.1159/000448597DOI Listing
September 2016

Human Herpesvirus Type 8-positive Multicentric Castleman Disease.

Clin Lymphoma Myeloma Leuk 2016 08 1;16 Suppl:S159-65. Epub 2016 Apr 1.

National Research Center for Hematology, Ministry of Healthcare of the Russian Federation, Moscow, Russia.

Castleman disease (CD) is rare lymphoproliferative disorder with local lesionsor with multiple lessions (multicentric CD [MCD]-usually with plasma cell or mix cell morphology). Patients with human herpesvirus (HHV) type 8-positive MCD were included in a separate group owing to its extremely aggressive course and the high risk of transformation into HHV8(+) plasmablastic lymphoma. At our hematologic center, from 1996 to the present, the clinical and morphologic features of 87 patients with CD were analyzed. Immunohistochemical examination revealed DNA HHV8(+) lymph node tissue in patients with plasma cell and mixed cell morphology. In 45 patients, plasma cell or mixed cell variant CD was diagnosed. In 21 patients (8%), the manifestation of CD was local and in 29 (9%), it was multicentric. HHV8 was identified in only 6 cases (23.1%) of MCD (5 men and 1 woman, with a median age of 48.2 years; range, 36-77 years). The median follow-up point was 39.2 months. In 4 patients, the mixed cell variant was diagnosed and in 2, the plasma cell variant was diagnosed. In all the patients, constitutional symptoms, generalized lymphadenopathy, and hepatosplenomegaly were detected. Various laboratory changes were observed, but the most significant were anemia, thrombocytopenia, hypergammaglobulinemia, M-component, increased erythrocyte sedimentation rate, and circulating immune complexes. In 2 cases of HHV8(+) CD, MCD was combined with autoimmune hemolytic anemia and in 2 cases with non-Hodgkin lymphoma. At the last follow-up point, 2 patients were still alive after CHOP (cyclophosphamide, prednisone, Adriamycin, vincristine) and R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], prednisone) therapy with rituximab maintenance. HHV8(+) MCD results in aggressive multiorgan lesions and pronounced changes in laboratory test results. It is characterized by an unfavorable prognosis with a high risk of transformation to plasmablastic lymphoma and a lethal outcome. Timely chemotherapy for patients with HHV8(+) MCD can result in remission and prolong life.
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http://dx.doi.org/10.1016/j.clml.2016.03.009DOI Listing
August 2016

Analysis of T-cell receptor-gamma gene rearrangements using oligonucleotide microchip: a novel approach for the determination of T-cell clonality.

J Mol Diagn 2007 Apr;9(2):249-57

Department of Biological Microchips, Engelhardt Institute of Molecular Biology, Moscow, Russia.

T-cell clonality estimation is important for the differential diagnosis between malignant and nonmalignant T-cell proliferation. Routinely used methods include polymerase chain reaction (PCR) analysis of T-cell receptor-gamma (TCR-gamma) gene rearrangements followed by Genescan analysis, polyacrylamide gel electrophoresis, or heteroduplex analysis to visualize amplification products. Here, we present a new method for the analysis after PCR of TCR-gamma rearrangements using hybridization on oligonucleotide microchip. A microchip was designed to contain specific probes for all functional variable (V) and joining (J) gene segments involved in rearrangements of the TCR-gamma locus. Fluorescently labeled fragments of rearranged gamma-chain from patients and donors were obtained in a multiplex nested PCR and hybridized with a microchip. The results were detected using a portable microchip analyzer. Samples from 49 patients with T-cell lymphomas or leukemias and 47 donors were analyzed for T-cell clonality by microchip and single-strand conformation polymorphism analysis, which served as a standard reference method. Comparison of two techniques showed full concordance of the results. The microchip-based approach also allowed the identification of V and J gene segments involved in the particular TCR-gamma rearrangement. The sensitivity of the method is sufficient to determine 10% of clonal cells in the sample.
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http://dx.doi.org/10.2353/jmoldx.2007.060087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867449PMC
April 2007