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The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic Leukemia

S. Urazbakhtin, A. Smirnova, A. Volakhava, E. Zerkalenkova, M. Salyutina, M. Doubek, H. Jelinkova, N. Khudainazarova, E. Volchkov, L. Belyaeva, E. Komech, S. Pavlova, Y. Lebedev, K. Plevova, Y. Olshanskaya, A. Komkov, I. Mamedov

. 2022 ; 23 (3) : . [pub] 20220203

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc22011069

Grant support
19-11299S Czech Science Foundation
075-15-2020-807 Ministry of Science and Higher Education of the Russian Federation

Retroelements (RE) have been proposed as important players in cancerogenesis. Different cancer types are characterized by a different level of tumor-specific RE insertions. In previous studies, small cohorts of hematological malignancies, such as acute myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia have been characterized by a low level of RE insertional activity. Acute lymphoblastic leukemia (ALL) in adults and childhood acute leukemias have not been studied in this context. We performed a search for new RE insertions (Alu and L1) in 44 childhood ALL, 14 childhood acute myeloid leukemia, and 14 adult ALL samples using a highly sensitive NGS-based approach. First, we evaluated the method sensitivity revealing the 1% detection threshold for the proportion of cells with specific RE insertion. Following this result, we did not identify new tumor-specific RE insertions in the tested cohort of acute leukemia samples at the established level of sensitivity. Additionally, we analyzed the transcription levels of active L1 copies and found them increased. Thus, the increased transcription of active L1 copies is not sufficient for overt elevation of L1 retrotranspositional activity in leukemia.

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$a Retroelements (RE) have been proposed as important players in cancerogenesis. Different cancer types are characterized by a different level of tumor-specific RE insertions. In previous studies, small cohorts of hematological malignancies, such as acute myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia have been characterized by a low level of RE insertional activity. Acute lymphoblastic leukemia (ALL) in adults and childhood acute leukemias have not been studied in this context. We performed a search for new RE insertions (Alu and L1) in 44 childhood ALL, 14 childhood acute myeloid leukemia, and 14 adult ALL samples using a highly sensitive NGS-based approach. First, we evaluated the method sensitivity revealing the 1% detection threshold for the proportion of cells with specific RE insertion. Following this result, we did not identify new tumor-specific RE insertions in the tested cohort of acute leukemia samples at the established level of sensitivity. Additionally, we analyzed the transcription levels of active L1 copies and found them increased. Thus, the increased transcription of active L1 copies is not sufficient for overt elevation of L1 retrotranspositional activity in leukemia.
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$a Volakhava, Anastasiya $u Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic
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$a Doubek, Michael $u Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic $u Institute of Medical Genetics and Genomics, University Hospital Brno and Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
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$a Jelinkova, Hana $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
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$a Volchkov, Egor $u Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia
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$a Belyaeva, Laima $u Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia
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$a Pavlova, Sarka $u Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
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$a Lebedev, Yuri $u Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia
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$a Olshanskaya, Yulia $u Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia
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$a Mamedov, Ilgar $u Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia $u Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic $u Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia $u Department of Molecular Technologies, Pirogov Russian National Research Medical University, 117997 Moscow, Russia $1 https://orcid.org/0000000239929285
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