ЛГ

Л. Г. Фечина

Institute of Medical Cell Technologies

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Grigory Tsaur

Regional Children's Clinical Hospital No. 1

АМ

А. М. Попов

National Research Center for Hematology Russian Academy of Medical Sciences

Tatiana Verzhbitskaya

Regional Children's Clinical Hospital No. 1

Egor Shorikov

Moscow City Oncology Hospital №62

Olga Streneva

Regional Children's Clinical Hospital No. 1

Leonid Saveliev

Ural State Medical University

Yulia Olshanskaya

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Alexander Karachunskiy

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Natalia Ponomareva

Russian Children's Clinical Hospital

Olga Aleinikova

Belarusian Research Center For Pediatric Oncology and Hematology

Cooperative Institutions

Ministry of Health of the Russian Federation

119

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

104

Regional Children's Clinical Hospital No. 1

Institute of Medical Cell Technologies

National Research Center for Hematology Russian Academy of Medical Sciences

Pirogov Russian National Research Medical University

Russian Children's Clinical Hospital

Inserm

Ural State Medical University

Russian Academy of Sciences

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Immunophenotyping in the diagnosis of acute leukemias of ambiguous lineage. The results of centralized diagnosis and practical guidelines

Pediatric Hematology/Oncology and Immunopathology (2024)

I. A. Demina Ekaterina Mikhailova Alexandra Semchenkova Tatiana Verzhbitskaya Zh. V. Permikin

Acute leukemias of ambiguous lineage (ALAL) are rare acute leukemias (AL) that exhibit specific features of more than one hematopoietic lineage or show no distinct evidence of lineage differentiation. Immunophenotyping plays a key role in the diagnosis and classification of ALAL. Despite the availability of diagnostic criteria for ALAL proposed by different expert groups, the accurate diagnosis of ALAL representing a rare and heterogeneous group of diseases remains a challenge. In this paper, we present a brief analysis of 97 pediatric ALAL cases. Such a large cohort of cases with ALAL (ALALs comprising less than 1 % of all pediatric AL) was obtained as a result of the centralized diagnosis of AL. With regard to the obtained results, we have developed the guidelines for the interpretation of the results of immunophenotyping in the diagnosis of ALAL and for the integration of findings from flow cytometry, cytomorphology and genetic testing for the accurate diagnosis and classification of this group of AL.

Immunophenotyping

Lineage (genetic)

10.24287/1726-1708-2024-23-1-219-230

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Suppressed miR-128-3p combined with TERT overexpression predicts dismal outcomes for neuroblastoma

Cancer Biomarkers (2022)

А. Е. Druy Grigory Tsaur Egor Shorikov Godelieve A.M. Tytgat Л. Г. Фечина

BACKGROUND: Molecular and clinical diversity of neuroblastomas is notorious. The activating TERT rearrangements have been associated with dismal prognosis. Suppression of miR-128-3p may complement and enhance the adverse effects of TERT overexpression. OBJECTIVE: The study aimed at evaluation of prognostic significance of the miR-128-3p/TERT expression in patients with primary neuroblastoma. METHODS: RNA samples isolated from fresh-frozen tumor specimens (n= 103) were reverse transcribed for evaluation of miR-128-3p and TERT expression by qPCR. The normalized expression levels were tested for correlations with the event-free survival (EFS). ROC-analysis was used to establish threshold expression levels (TLs) for the possible best prediction of the outcomes. The median follow-up was 57 months. RESULTS: Both TERT overexpression and miR-128-3p downregulation were independently associated with superior rates of adverse events (p= 0.027, TL =-2.32 log10 and p= 0.080, TL =-1.33 log10, respectively). The MYCN single-copy patients were stratified into groups based on the character of alterations in expression of the studied transcripts. Five-year EFS in the groups of patients with elevated TERT/normal miR-128-3p expression and normal TERT/reduced miR-128-3p expression were 0.74 ± 0.08 and 0.60 ± 0.16, respectively. The patients with elevated TERT/reduced miR-128-3p expression had the worst outcomes, with 5-year EFS of 0.40 ± 0.16 compared with 0.91 ± 0.06 for the patients with unaltered levels of both transcripts (p< 0.001). Cumulative incidence of relapse/progression for the groups constituted 0.23 ± 0.08, 0.40 ± 0.16, 0.60 ± 0.16 and 0.09 ± 0.06, respectively. Moreover, the loss of miR-128-3p was qualified as independent adverse predictor which outperformed the conventional clinical and genetic risk factors in the multivariate Cox regression model of EFS. CONCLUSIONS: Combined expression levels of miR-128-3p and TERT represent a novel prognostic biomarker for neuroblastoma.

10.3233/cbm-210414

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Использование флюоресцентной гибридизации in situ для выявления транслокации (6;11)(q27;q23): описание 3 случаев

Oncohematology (2008)

Olga Plekhanova Grigory Tsaur А. С. Иванова Л И Савельев Л. Г. Фечина

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Prognostic value of initial bone marrow disease detection by multiparameter flow cytometry in children with neuroblastoma

Journal of Cancer Research and Clinical Oncology (2019)

А. М. Попов А. Е. Druy Egor Shorikov Tatiana Verzhbitskaya Alexander Solodovnikov

Immunophenotyping

Hematology

Cumulative incidence

Clinical Significance

10.1007/s00432-018-02831-w

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The comparative analysis of BCR-ABL/ABL detection by real-time quantitative PCR and automated GeneXpert Dx System in chronic myeloid leukemia patients with major and complete molecular response

DOAJ (DOAJ: Directory of Open Access Journals) (2014)

Svetlana Smirnikhina Grigory Tsaur Ekaterina Chelysheva Yu. A. Yakovleva А. В. Лавров

GeneXpert MTB/RIF

ABL

10.17650/1818-8346-2013-8-3-16-21

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Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene

Almanac of Clinical Medicine (2023)

O. V. Koryakina О. П. Ковтун Grigory Tsaur Elena V. Tsyganko Л. Г. Фечина

Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy. Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed. Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.415.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found. Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy.

Acute lymphocytic leukemia

10.18786/2072-0505-2023-51-016

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ИССЛЕДОВАНИЕ СТРУКТУРЫ ХИМЕРНЫХ ГЕНОВ С УЧАСТИЕМ ГЕНА MLL ПРИ ОСТРЫХ ЛЕЙКОЗАХ У ДЕТЕЙ ПЕРВОГО ГОДА ЖИЗНИ

Гематология и трансфузиология (2014)

Цаур Григорий Анатольевич Claus Meyer А. М. Попов Olga Plekhanova Anatoly Kustanovich

Р е з ю м е. Целью данной работы являлось описание механизмов образования химерных генов с вовлечением гена MLL у детей первого года жизни, больных острыми лейкозами, у которых методом длинной инвертированной полимеразной цепной реакции (ДИ-ПЦР) в ДНК выявлена перестройка гена MLL. В исследование были включены 72 больных в возрасте от 1 дня до 11 мес, в том числе 52 больных острым лимфобластным лейкозом (ОЛЛ), 19 больных острым миелоидным лейкозом (ОМЛ), 1 больной острым недифференцированным лейкозом. При ОЛЛ наиболее частым (53,8%) химерным геном являлся MLL-AF4, реже выявлялись MLL-MLLT1 (23,1%), MLL-MLLT3 (13,5%), MLL-EPS15 (7,7%), MLL-AFF3 (1,9%). При ОМЛ самым часто выявляемым (36,8%) химерным геном был MLL-MLLT3, реже (26,3%) были найдены MLL-MLLT10, MLL-MLLT11 и MLL-MYO1F (по 10,5%), MLL-AF4, а также MLL-SEPT6 и MLL-SEPT9 (по 5,3%). Наиболее частой зоной разрыва в ДНК гена MLL при ОЛЛ являлся 11-й интрон, на долю которого приходилось 48,1% случаев, а при ОМЛ — это 9-й интрон (42,1%). Больные ОЛЛ, у которых точка разрыва располагалась в 11-м интроне, были младше всех остальных (p = 0,025). Не обнаружено связи между локализацией точек разрыва и полом больного, уровнем инициального лейкоцитоза и типом гена-партнера. Зоны разрыва в генах-партнерах MLL чаще всего затрагивали один или два интрона, за исключением генов AF4 и MLLT10, в которых зоны разрывов более протяженные. Самым частым механизмом образования химерных генов с участием MLL являлась реципрокная транслокация (73,6%), значительно реже — транс-сплайсинг (15,3%) или инсерции (11,1%). С помощью ДИ-ПЦР были найдены такие редкие гены-партнеры MLL, как AFF3, MYO1F, SEPT6, SEPT9, а также нетипичные локализации точек разрыва при наличии MLL-AF4: 7-й интрон гена MLL и 10-й интрон гена AF4, не выявляемые стандартной ПЦР с обратной транскрипцией. Таким образом, нами детально охарактеризована структура химерных генов с участием MLL в большой группе детей первого года жизни, больных острыми лейкозами. Ключевые слова : острый лейкоз; дети первого года жизни; перестройки гена MLL; полимеразная цепная реакция.

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A Single Dose of PEG-Asparaginase at the Beginning of Induction Not Only Accelerates MRD Clearance but Also Improves Long-Term Outcome in Children with B-Lineage ALL

Cancers (2023)

А. М. Попов Günter Henze Julia Roumiantseva Oleh Bydanov Mikhail Belevtsev

This report presents the results of the assessment of MRD response by multicolor flow cytometry (MFC) with regard to the randomized use of pegylated asparaginase (PEG). In this study, PEG was randomly administered at a dose of 1000 U/m2 on day 3 of induction therapy in children with B-lineage ALL. Methods. Conventional induction therapy consisted of dexamethasone, vincristine, and daunorubicin. MRD data was available in 502 patients who were randomized at the start of induction therapy, standard-risk (SR) patients into three (conventional induction without PEG, induction with additional PEG and with PEG but without daunorubicin) and intermediate-risk (ImR) patients into two groups (with additional PEG and without PEG). Results. The single administration of PEG resulted in a significantly higher proportion of rapid responders, in SR patients even when no anthracyclines were used for induction. In the SR group, the event-free survival of the MFC-MRD fast responders was similar in the PEG− and PEG+ arms (92.0 ± 3.1% vs. 96.2 ± 1.5%, respectively), and the same unfavorable trend was observed for MFC-MRD slow responders (57.5 ± 12.3% vs. 66.7 ± 15.7%, respectively). Results were similar in ImR patients: (94.3 ± 3.2% vs. 95.1 ± 2.4%, for fast responders and 63.3 ± 7.6% vs. 78.1 ± 7.9%, for slow responders in PEG− and PEG+ arms, respectively). However, there is a large difference between the proportion of MFC-MRD slow responders in the PEG− and PEG+ groups (18.3% vs. 5.2% for the SR group and 44.2% vs. 25.0% for the ImR group). Conclusions. Therefore, early use of PEG-ASP not only leads to an accelerated reduction of blasts, but also to an excellent outcome in a significantly larger proportion of patients in both risk groups.

Daunorubicin

Asparaginase

10.3390/cancers15235547

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Inﬂuence of value of minimal residual disease at risk of developing recurrence of relapse in patients with acute lymphoblastic leukemia

Proceedings of the National Academy of Sciences of Belarus Medical series (2019)

E. A. Stolyarova N. V. Migal Mikhail Belevtsev Л. В. Мовчан O. I. Budanov

Minimal residual disease (MRD) is the most significant predictor of the relapse in patients with acute lymphoblastic leukemia (ALL). MRD evaluation is necessary not only for the prediction of the relapse, but for additional stratification of patients by the risk groups in order to address the issue of the therapy individualization and to evaluate the therapy quality. This study analyzes the MRD parameters in patients with ALL at the stage of induction therapy and evaluates the eﬀect of the value of the minimum residual disease on survival rates and the risk of relapse in patients with ALL treated according to protocol ALL-MB 2008.

Minimal Residual Disease

Risk Stratification

10.29235/1814-6023-2019-16-2-202-215

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MLL Gene Rearrangements in 174 Infants with Acute Leukemia.

Blood (2012)

Grigory Tsaur А. М. Попов Е. В. Флейшман Sokova Oi Anna Demina

Breakpoint

Gene rearrangement

10.1182/blood.v120.21.2537.2537

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