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

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...

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Main Authors: Shamil Urazbakhtin, Anastasia Smirnova, Anastasiya Volakhava, Elena Zerkalenkova, Maria Salyutina, Michael Doubek, Hana Jelinkova, Nelly Khudainazarova, Egor Volchkov, Laima Belyaeva, Ekaterina Komech, Sarka Pavlova, Yuri Lebedev, Karla Plevova, Yulia Olshanskaya, Alexander Komkov, Ilgar Mamedov
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/3/1756
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author Shamil Urazbakhtin
Anastasia Smirnova
Anastasiya Volakhava
Elena Zerkalenkova
Maria Salyutina
Michael Doubek
Hana Jelinkova
Nelly Khudainazarova
Egor Volchkov
Laima Belyaeva
Ekaterina Komech
Sarka Pavlova
Yuri Lebedev
Karla Plevova
Yulia Olshanskaya
Alexander Komkov
Ilgar Mamedov
author_facet Shamil Urazbakhtin
Anastasia Smirnova
Anastasiya Volakhava
Elena Zerkalenkova
Maria Salyutina
Michael Doubek
Hana Jelinkova
Nelly Khudainazarova
Egor Volchkov
Laima Belyaeva
Ekaterina Komech
Sarka Pavlova
Yuri Lebedev
Karla Plevova
Yulia Olshanskaya
Alexander Komkov
Ilgar Mamedov
author_sort Shamil Urazbakhtin
collection DOAJ
description 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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spelling doaj.art-aec214d68e734440b5bfd03bb30f4a6b2023-11-23T16:46:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233175610.3390/ijms23031756The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic LeukemiaShamil Urazbakhtin0Anastasia Smirnova1Anastasiya Volakhava2Elena Zerkalenkova3Maria Salyutina4Michael Doubek5Hana Jelinkova6Nelly Khudainazarova7Egor Volchkov8Laima Belyaeva9Ekaterina Komech10Sarka Pavlova11Yuri Lebedev12Karla Plevova13Yulia Olshanskaya14Alexander Komkov15Ilgar Mamedov16Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaDepartment of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaCentral European Institute of Technology, Masaryk University, 625 00 Brno, Czech RepublicDmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, RussiaDepartment of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaCentral European Institute of Technology, Masaryk University, 625 00 Brno, Czech RepublicDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 625 00 Brno, Czech RepublicDepartment of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaDmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, RussiaDmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, RussiaDepartment of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaCentral European Institute of Technology, Masaryk University, 625 00 Brno, Czech RepublicDepartment of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaCentral European Institute of Technology, Masaryk University, 625 00 Brno, Czech RepublicDmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, RussiaDepartment of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaDepartment of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, RussiaRetroelements (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.https://www.mdpi.com/1422-0067/23/3/1756acute leukemiaretroelementsmobile elementstumor-specific insertions
spellingShingle Shamil Urazbakhtin
Anastasia Smirnova
Anastasiya Volakhava
Elena Zerkalenkova
Maria Salyutina
Michael Doubek
Hana Jelinkova
Nelly Khudainazarova
Egor Volchkov
Laima Belyaeva
Ekaterina Komech
Sarka Pavlova
Yuri Lebedev
Karla Plevova
Yulia Olshanskaya
Alexander Komkov
Ilgar Mamedov
The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic Leukemia
International Journal of Molecular Sciences
acute leukemia
retroelements
mobile elements
tumor-specific insertions
title The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic Leukemia
title_full The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic Leukemia
title_fullStr The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic Leukemia
title_full_unstemmed The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic Leukemia
title_short The Absence of Retroelement Activity Is Characteristic for Childhood Acute Leukemias and Adult Acute Lymphoblastic Leukemia
title_sort absence of retroelement activity is characteristic for childhood acute leukemias and adult acute lymphoblastic leukemia
topic acute leukemia
retroelements
mobile elements
tumor-specific insertions
url https://www.mdpi.com/1422-0067/23/3/1756
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