Publications by authors named "Yulia Olshanskaya"

19 Publications

  • Page 1 of 1

Blinatumomab following haematopoietic stem cell transplantation - a novel approach for the treatment of acute lymphoblastic leukaemia in infants.

Br J Haematol 2021 Apr 11. Epub 2021 Apr 11.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.

Blinatumomab with subsequent haematopoietic stem cell transplantation was applied in 13 infants with acute lymphoblastic leukaemia (ALL). Eight patients were treated in first remission due to slow clearance of minimal residual disease (MRD); one for MRD-reappearance after long MRD negativity, one for primary refractory disease and three during relapse treatment. In slow MRD responders, complete MRD response was achieved prior to transplantation, with an 18-month event-free survival of 75%. In contrast, only one of five patients with relapsed/refractory ALL is still in complete remission. These data provide a basis for future studies of immunotherapy in very high-risk infant ALL.
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http://dx.doi.org/10.1111/bjh.17466DOI Listing
April 2021

Relative expansion of CD19-negative very-early normal B-cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR-T cell therapy: implications for flow cytometric detection of minimal residual disease.

Br J Haematol 2021 May 14;193(3):602-612. Epub 2021 Mar 14.

National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.

CD19-directed treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP-ALL is based on B-cell compartment study, CD19 loss could hamper MFC-MRD monitoring after blinatumomab or chimeric antigen receptor T-cell (CAR-T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B-lineage gating markers allows the identification of CD19-negative leukaemia, but it could also lead to misidentification of normal very-early CD19-negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19-negative normal BCPs in 106 children with BCP-ALL who underwent CD19 targeting (blinatumomab, n = 64; CAR-T, n = 25; or both, n = 17). It was found that normal CD19-negative BCPs could be found in bone marrow after CD19-directed treatment more frequently than in healthy donors and children with BCP-ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19-negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC-MRD more accurately in patients who have undergone CD19-targeted therapy, even in cases with normal CD19-negative BCP expansion.
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http://dx.doi.org/10.1111/bjh.17382DOI Listing
May 2021

GATA1 mutation analysis and molecular landscape characterization in acute myeloid leukemia with trisomy 21 in pediatric patients.

Int J Lab Hematol 2021 Jan 2. Epub 2021 Jan 2.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Introduction: Accurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions.

Methods: The DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high-throughput sequencing (HTS).

Results: Acquired GATA1 mutations were identified in 43 cases (98%). Additional mutations in the genes of JAK/STAT signaling, cohesin complex, and RAS pathway activation were revealed by HTS in 48%, 36%, and 16% of the cases, respectively.

Conclusions: The GATA1 mutations were reliably determined by fragment analysis and/or Sanger sequencing in a single PCR amplicon manner. For patients with extremely low blast counts and/or rare variants, the rapid screening with simple molecular approaches must be complemented with HTS. The JAK/STAT and RAS pathway-activating mutations may represent an extra option of targeted therapy with kinase inhibitors.
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http://dx.doi.org/10.1111/ijlh.13451DOI Listing
January 2021

Immunophenotypic changes of leukemic blasts in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia, who have been treated with Blinatumomab.

Haematologica 2020 12 30;Online ahead of print. Epub 2020 Dec 30.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology; 1 Samory Mashela St., Moscow 117998, Russian Federation.

Not available.
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http://dx.doi.org/10.3324/haematol.2019.241596DOI Listing
December 2020

Additional flow cytometric studies for differential diagnosis between Burkitt lymphoma/leukemia and B-cell precursor acute lymphoblastic leukemia.

Leuk Res 2021 01 8;100:106491. Epub 2020 Dec 8.

National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela St., 117998, Moscow, Russia. Electronic address:

The differentiation between Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is sometimes complicated. Laboratory findings that favor BL (e.g., surface expression of μ heavy chain and/or one of the light chains of immunoglobulin, FAB L3 morphology of blasts, MYC gene rearrangements) are not always present simultaneously. Our previous work demonstrated that BL differed from Ig(+) BCP-ALL by expression of Ig and other surface markers. In the current study, we have evaluated additional flow cytometric markers for reliable differentiation between BL and BCP-ALL. Among three studied surface antigens (CD44, CD38, CD58), only CD58 demonstrated significantly higher expression in BL as compared to BCP-ALL. Moreover, BL cases were associated with an increased level of Ki-67 and a higher percentage of cells in the S-phase of cell cycle. These two features reflect an aggressive proliferative potential of BL. Thus, when BL is suspected and results of surface Ig evaluation are controversial, the flow cytometric analysis of CD58, Ki-67 and cell cycle could assist in the differential diagnosis.
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http://dx.doi.org/10.1016/j.leukres.2020.106491DOI Listing
January 2021

Quantification of NG2-positivity for the precise prediction of KMT2A gene rearrangements in childhood acute leukemia.

Genes Chromosomes Cancer 2021 Feb 20;60(2):88-99. Epub 2020 Nov 20.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

It has long been known that there is a link between neuron glial antigen 2 (NG2) surface expression and KMT2A gene rearrangements in acute leukemia (AL). However, the exact levels of NG2 positivity that predict the presence of KMT2A rearrangement are not known. The current study focuses on a cohort of 505 pediatric AL patients who showed any level of positive NG2 expression (greater than 1% of cells) for whom comprehensive genetic data were available. NG2 expression was measured as either the percentage of positive cells or the number of molecules on the cell surface. KMT2A gene rearrangements were identified by FISH. The fusion partner was detected with RT-PCR, LDI-PCR or anchored multiplex PCR followed by high-throughput sequencing. KMT2A-positive samples comprised a substantial proportion of the NG2-positive cohort (180 of 505, 36%), with a total of 19 different types of translocation. Despite its occurrence in other AL genetic subgroups, NG2 expression was significantly increased in AL patients with KMT2A rearrangements in terms of both the cell percentage and number of molecules per cell. The threshold levels (TL) for NG2-positivity were established by ROC analysis of the whole cohort and separately for children less than 1 years old and older with lymphoblastic (ALL) and myeloid (AML) leukemia. The lowest TL was defined in infants with ALL (7%), while in older children, the threshold was higher (12%). In AML patients, the situation was reversed, with 28% NG2-positivity in infants and 14% in patients >1 year old. The defined TLs resulted in improved diagnostic performance compared to the conventional thresholds of 10% and 20% for all patient groups.
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http://dx.doi.org/10.1002/gcc.22915DOI Listing
February 2021

High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies.

Br J Haematol 2020 03 6;188(5):723-731. Epub 2019 Oct 6.

Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.

Rearrangements of T- and B-cell receptor (TCR and BCR) genes are useful markers for clonality assessment as well as for minimal residual disease (MRD) monitoring during the treatment of haematological malignancies. Currently, rearrangements of three out of four TCR and all BCR loci are used for this purpose. The fourth TCR gene, TRA, has not been used so far due to the lack of a method for its rearrangement detection in genomic DNA. Here we propose the first high-throughput sequencing based method for the identification of clonal TRA gene rearrangements at the DNA level. The method is based on target amplification of the rearranged TRA locus using an advanced multiplex polymerase chain reaction system and high-throughput sequencing, and has been tested on DNA samples from peripheral blood of healthy donors. Combinations of all functional V- and J-segments were detected, indicating the high sensitivity of the method. Additionally, we identified clonal TRA rearrangements in 57 out of 112 tested DNA samples of patients with various T-lineage lymphoproliferative disorders. The method fills the existing gap in utilizing the TRA gene for a wide range of studies, including clonality assessment, MRD monitoring and clonal evolution analysis in different lymphoid malignancies.
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http://dx.doi.org/10.1111/bjh.16230DOI Listing
March 2020

Heterogeneity of childhood acute leukemia with mature B-cell immunophenotype.

J Cancer Res Clin Oncol 2019 Nov 28;145(11):2803-2811. Epub 2019 Aug 28.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela St., GSP-7, Moscow, 117997, Russia.

Background: Flow cytometry (FCM) plays a crucial role in the differential diagnosis of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The presence of surface IgM (sIgM) alone or with light chain restriction indicates a mature blast phenotype (BIV by EGIL) and is usually observed in BL. However, sIgM expression could also be detected in transitional BCP-ALL cases. These similarities in immunophenotype and ambiguous correspondence with other laboratory findings may challenge the correct BL diagnostics.

Methods: We retrospectively reviewed the available data from immunophenotypic, morphological, cytogenetic, and molecular genetic studies of 146 children (85 boys and 61 girls) with a median age of 10 years (range 0-18 years) who were diagnosed with BL and BCP-ALL. The blasts' immunophenotype was studied by multicolor FCM. The conventional cytogenetic analysis included G-banded karyotyping and fluorescence in situ hybridization (FISH).

Results: In 54 children classified as BIV-ALL according to the EGIL, it was demonstrated that sIgM in a minority of cases can be associated with various types of BCP-ALL. Analysis of the antigen expression profile of 105 patients with verified BL (n = 21) and BCP-ALL (n = 84) showed significant differences in BL and the sIgM(+) vs BCP-ALL immunophenotype. Thus, even in cases of ambiguous sIgM expression, these two diseases could be reliably discriminated by complex immunophenotyping. Moreover, 10 patients (7 boys and 3 girls) with BL leukemic cells did not express sIgM, and they were diagnosed with BL on the basis of other laboratory and clinical signs.

Conclusions: In conclusion, our study shows that BIV subtype is heterogeneous group of leukemia including not only the BL, but also BCP-ALL. In ambiguous cases, only a combination of multiple immunophenotypic, cytomorphologic, and genetic diagnostic technologies can allow the precise discrimination of BL and BCP-ALL and selection of the appropriate treatment scheme.
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http://dx.doi.org/10.1007/s00432-019-03010-1DOI Listing
November 2019

Outcome of αβ T cell-depleted transplantation in children with high-risk acute myeloid leukemia, grafted in remission.

Bone Marrow Transplant 2020 01 15;55(1):256-259. Epub 2019 Apr 15.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Medical Research Сenter of Pediatric Hematology, Oncology and Immunology, Samory Mashela street, 1, Moscow, 117997, Russia.

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http://dx.doi.org/10.1038/s41409-019-0531-3DOI Listing
January 2020

αβ T Cell-Depleted Haploidentical Hematopoietic Stem Cell Transplantation without Antithymocyte Globulin in Children with Chemorefractory Acute Myelogenous Leukemia.

Biol Blood Marrow Transplant 2019 05 21;25(5):e179-e182. Epub 2019 Jan 21.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Moscow, Russia. Electronic address:

We evaluated the outcome of αβ T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory acute myelogenous leukemia (AML). Twenty-two patients with either primary refractory (n = 10) or relapsed refractory (n = 12) AML in active disease status received a transplant from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent myeloablative conditioning with treosulfan and thiotepa. Antithymocyte globulin was substituted with tocilizumab in all patients and also with abatacept in 10 patients. Grafts were peripheral blood stem cells engineered by αβ T cell and CD19 depletion. Post-transplantation prophylactic therapy included infusion of donor lymphocytes, composed of a CD45RA-depleted fraction with or without a hypomethylating agent. Complete remission was achieved in 21 patients (95%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 18%, and the cumulative incidence of chronic GVHD was 23%. At 2 years, transplantation-related mortality was 9%, relapse rate was 42%, event-free survival was 49%, and overall survival was 53%. Our data suggest that αβ T cell-depleted haploidentical HSCT provides a reasonable chance of long-term survival in a cohort of children with chemorefractory AML and creates a solid basis for further improvement.
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http://dx.doi.org/10.1016/j.bbmt.2019.01.023DOI Listing
May 2019

Acute myeloid leukemia with t(10;11)(p11-12;q23.3): Results of Russian Pediatric AML registration study.

Int J Lab Hematol 2019 Apr 9;41(2):287-292. Epub 2019 Jan 9.

Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Introduction: Translocations involving the KMT2A gene (also known as MLL) are frequently diagnosed in pediatric acute leukemia cases with either lymphoblastic or myeloid origin. KMT2A is translocated to multiple partner genes, including MLLT10/AF10 localizing at chromosomal band 10p12. KMT2A-MLLT10 is one of the common chimeric genes diagnosed in acute leukemia with KMT2A rearrangement (8%), especially in acute myeloid leukemia (AML; 18%). MLLT10 is localized in very close proximity to two other KMT2A partner genes at 10p11-12-NEBL and ABI1, so they could not be distinguished by conventional cytogenetics.

Methods: In this work, we present a cohort of 28 patients enrolled into Russian Pediatric AML registration study carrying rearrangements between chromosomal regions 11q23.3 and 10p11-12. G-banding, FISH, reverse transcription PCR, and long-distance inverse PCR were used to characterize the KMT2A gene rearrangements in these patients.

Results: We demonstrate that 25 patients harbor the KMT2A-MLLT10 rearrangement, while three patients show the rare KMT2A rearrangements (2× KMT2A-NEBL; 1× KMT2A-ABI1).

Conclusions: Therefore, the combination of cytogenetic and molecular genetic methods is of high importance in diagnosing cases with t(10;11)(p11-12;q23.3).
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http://dx.doi.org/10.1111/ijlh.12969DOI Listing
April 2019

A case of pediatric acute myeloid leukemia with t(11;16)(q23;q24) leading to a novel KMT2A-USP10 fusion gene.

Genes Chromosomes Cancer 2018 10 14;57(10):522-524. Epub 2018 Aug 14.

Laboratory of Cytogenetics and Molecular Genetics, Dmitry Rogachev Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

We present a leukemia case that exhibits a chromosomal translocation t(11;16)(q23;q23), which results in the expression of a novel KMT2A fusion gene. This novel fusion, KMT2A-USP10, was found in a relapse of acute myeloid leukaemia M5a. USP10 belongs to a protein family that deubiquitinates a distinct set of target proteins, and thus, increases the steady state protein levels of its target subproteome. One of the USP10 targets is TP53. Wildtype TP53 is usually rescued from proteasomal degradation by USP10. As most KMT2A leukemias display wildtype p53 alleles, one might argue that the disruption of an USP10 allele can be classified as a pro-oncogenic event.
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http://dx.doi.org/10.1002/gcc.22646DOI Listing
October 2018

Clinical significance of cytogenetic changes in childhood T-cell acute lymphoblastic leukemia: results of the multicenter group Moscow-Berlin (MB).

Leuk Lymphoma 2019 02 1;60(2):426-432. Epub 2018 Aug 1.

i Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Charité CVK, Universitätsmedizin Berlin , Berlin , Germany.

The prognostic significance of genetic lesions in T-cell ALL still needs to be elucidated. Karyotyping and FISH were performed in samples from 120 patients with T-cell ALL registered in the trial Moscow-Berlin 2008. Most frequent rearrangements were TLX3 (N = 29; 24%) and TAL1 (N = 18; 15%), followed by KMT2A (N = 6; 5%), TLX1 (N = 5; 4.2%), and 11p13-15 (N = 5; 4.2%). In 16.7% of patients, the karyotype was normal, and in 30.8% 'other' aberrations were seen. Patients with a normal karyotype, TAL1, or KMT2A rearrangements had the most favorable outcome (probability of event free survival (pEFS): 82% ± 6%), while prognosis for patients with TLX3 and TLX1 rearrangements and 'other' aberrations was less favorable (pEFS: 62% ± 6%). Worst outcome was observed for five patients with 11p rearrangements (pEFS: 20% ± 18%). In summary, three subgroups of patients with T-cell ALL with significantly different outcomes could be defined by cytogenetic profiling.
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http://dx.doi.org/10.1080/10428194.2018.1485904DOI Listing
February 2019

Molecular characteristic of acute leukemias with t(16;21)/FUS-ERG.

Ann Hematol 2018 Jun 9;97(6):977-988. Epub 2018 Feb 9.

Dmitry Rogachev Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samora Mashela str., 1, Moscow, 117997, Russia.

T(16;21)(p11;q22)/FUS-ERG is a rare but recurrent translocation in acute leukemias and in some types of solid tumors. Due to multiple types of FUS-ERG transcripts, PCR-based minimal residual disease detection is impeded. In this study, we evaluated a cohort of pediatric patients with t(16;21)(p11;q22)/FUS-ERG and revealed fusion gene breakpoints. We implemented next-generation sequencing (NGS) on long PCR amplicons for the detection of fusion genes with unknown partners or DNA breakpoints. That allowed us to describe different fusion variants of FUS/ERG in different patients and to detect MRD on both RNA and DNA levels. We also found several accompanying mutations in epigenetic regulators (DNMT3A, ASXL1, BCOR) by targeted NGS approach in AML cases. These mutations preceded full transformation by t(16;21)(p11;q22)/FUS-ERG and allowed us to trace clonal evolution on all steps of therapy. As a casual observation, the ASXL1 mutation was found in the unrelated donor hematopoietic cells.
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http://dx.doi.org/10.1007/s00277-018-3267-zDOI Listing
June 2018

A new variant of KMT2A(MLL)-FLNA fusion transcript in acute myeloid leukemia with ins(X;11)(q28;q23q23).

Cancer Genet 2015 Apr 7;208(4):148-51. Epub 2015 Mar 7.

Federal Scientifc Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

The KMT2A gene (previously known as MLL) located at 11q23 is often involved in recurrent chromosomal translocations that lead to the development of acute leukemia, particularly in infants. Acute leukemias with KMT2A rearrangements have different prognoses, which depend on the partner gene involved in the translocation. The detection of all possible types of KMT2A gene rearrangements is of key importance for the identification of biological subgroups, which may differ in clinical outcome. In this report, we describe a case study of a 7-month-old boy who presented with AML-M4; however, no obvious 11q23 rearrangement was detected in the analyzed karyotype. Fluorescence in situ hybridization evaluation showed a nonstandard signal distribution in blast cells, corresponding to the presence of two KMT2A copies and one additional copy of 5'-KMT2A inserted into the long arm of the X chromosome (ins(X;11)(q28;q23q23)). Subsequent molecular analysis showed a novel variant form of the previously described KMT2A-FLNA fusion gene, in which the KMT2A intron 9 is fused to the FLNA exon 16.
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http://dx.doi.org/10.1016/j.cancergen.2015.03.001DOI Listing
April 2015

Immunohistochemistry, fluorescence in situ hybridization, and reverse transcription-polymerase chain reaction for the detection of anaplastic lymphoma kinase gene rearrangements in patients with non-small cell lung cancer: potential advantages and methodologic pitfalls.

Arch Pathol Lab Med 2014 Jun;138(6):794-802

From the Laboratory of Molecular Diagnostics (Drs Demidova and Gagarin and Mr Barinov), the Departments of Pathology (Drs Savelov and Grinevitch), Chemotherapy (Dr Stroiakovaski), and Thoracic Surgery (Dr Popov), Moscow Oncological Hospital 62, Moscow, Russia; the Departments of Thoracic Oncology (Dr Laktionov) and Chemotherapy (Dr Gutorov), N. N. Blokhin Russian Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia; the Department of Radiology, N. N. Burdenko Central Military Hospital, Moscow, Russia (Dr Smolin); the Laboratory of Cytogenetics and Molecular Genetics, Russian Federal Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia (Ms Olshanskaya); and the Laboratory of Cytogenetics, Russian Scientific Center for Hematology, Moscow, Russia (Ms Obukhova).

Context: Echinoderm microtubule-associated protein-like 4 gene (EML4) and anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of tumorigenesis in approximately 3% to 5% of patients with non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib. However, no complete agreement regarding the best diagnostic test for identification of ALK rearrangements has been achieved yet.

Objective: To investigate the concordance, sensitivity, and specificity of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription-polymerase chain reaction (RT-PCR) for detection of ALK rearrangements.

Design: Thirty-six prospectively tested patients with NSCLC who had adenocarcinoma and 10 ALK-positive samples were included in the study. All samples were tested by IHC (ALK1 clone, 5A4 clone, D5F3 clone), FISH (LSI ALK Break Apart and ALK FISH Probe), and multiplexed RT-PCR.

Results: Immunohistochemistry staining was successful in all samples.. Clone D5F3 showed the best sensitivity and specificity of 100%; clones ALK1 and 5A4 showed sensitivities of 91% with specificity of 100%. Both FISH probes showed concordance with sensitivity and specificity of 100%. Hybridization and RT-PCR were successful in 98% and 93.4% of samples, respectively, with sensitivity of 88% and specificity of 100%. Frequent artifacts leading to misinterpretation were observed with all 3 methodologies.

Conclusions: All 3 methodologies showed good sensitivity, specificity, and concordance, when artifacts were characterized and excluded. However, all ambiguous cases have to be confirmed as ALK rearranged by at least 2 of the 3 methods.
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http://dx.doi.org/10.5858/arpa.2012-0762-OADOI Listing
June 2014

Myelodysplastic syndromes with isolated deletion of the long arm of the chromosome X as a sole cytogenetic change.

Cancer Genet Cytogenet 2006 May;167(1):47-50

Hematological Scientific Center, Novozykovsky pr. 4 A, 125167 Moscow, Russia.

Deletions of Xq are extremely rare events in myelodysplastic syndromes (MDS) patients and were previously described in five patients, in two of them as a sole chromosome abnormality. We found isolated del(Xq) in 3 of 127 MDS patients with clonal chromosome changes. Detailed analysis of clinical and morphological data of presented and previously published cases indicates the following: (1) del(X)(q24) and del(X)(q13) are nonrandom chromosomal abnormalities in MDS; (2) MDS with deletions of Xq affect exclusively females ages 46-65; and (3) deletions of Xq are associated with refractory anemia with excess blasts (RAEB) and indicate an unfavorable prognosis.
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http://dx.doi.org/10.1016/j.cancergencyto.2005.08.018DOI Listing
May 2006

Neoplastic transformation is not the cause of extremely long (more than 100 weeks) hematopoiesis maintenance of long-term bone marrow culture from TNF-deficient mice.

Hematol J 2003 ;4(1):74-7

Hematological Scientific Center, Moscow, Russia.

Total cell production and longevity of hematopoiesis in long-term bone marrow culture of tumor necrosis factor (TNF)-deficient mice (LTBM-TNFko) are increased. The rate of apoptosis is decreased during the first 40 weeks in culture, then the level of apoptosis reaches levels of wild-type cultures. Extended lifespan of primary cultures usually is the consequence of the neoplastic transformation. We set out to check this possibility in the LTBM-TNFko. Telomerase activity in suspension fraction (SF) of LTBM-TNFko increases with time and reaches maximum a year after culture initiation. Cytogenetic study reveals genome instability in SF and hyperploidy in the adhesion cell layer (ACL) of LTBM-TNFko. All of the above indicate the possibility of neoplastic transformation. However, histological study of cells and CFU-S-derived colonies of SF does not reveal a block of differentiation. Cells of SF are unable to grow without ACL. Although those cells could proliferate in the presence of exogenous growth factors, they are not able to be passaged. Attempts of passaging ACL cells failed as well. Neither healthy nor sublethally irradiated recipients injected intravenously or intraperitoneally with cells of SF develop tumors within 8 months of observation. In conclusion, abnormal dynamics of long-term bone marrow culture of TNF-deficient mice could not be explained by neoplastic transformation.
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http://dx.doi.org/10.1038/sj.thj.6200203DOI Listing
July 2003