Cancers (Nov 2023)
Prognostic Impact of Copy Number Alterations’ Profile and AID/RAG Signatures in Acute Lymphoblastic Leukemia (ALL) with BCR::ABL and without Recurrent Genetic Aberrations (NEG ALL) Treated with Intensive Chemotherapy
- Marta Libura,
- Karolina Karabin,
- Paweł Tyrna,
- Anna Czyż,
- Hanna Makuch-Łasica,
- Bożena Jaźwiec,
- Monika Paluszewska,
- Beata Piątkowska-Jakubas,
- Magdalena Zawada,
- Michał Gniot,
- Joanna Trubicka,
- Magdalena Szymańska,
- Katarzyna Borg,
- Marta Więsik,
- Sylwia Czekalska,
- Izabela Florek,
- Maria Król,
- Małgorzata Paszkowska-Kowalewska,
- Lidia Gil,
- Katarzyna Kapelko-Słowik,
- Elżbieta Patkowska,
- Agnieszka Tomaszewska,
- Krzysztof Mądry,
- Rafał Machowicz,
- Tomasz Czerw,
- Agnieszka Piekarska,
- Magdalena Dutka,
- Anna Kopińska,
- Grzegorz Helbig,
- Tomasz Gromek,
- Krzysztof Lewandowski,
- Marta Zacharczuk,
- Anna Pastwińska,
- Tomasz Wróbel,
- Olga Haus,
- Grzegorz Basak,
- Jerzy Hołowiecki,
- Przemysław Juszczyński,
- Ewa Lech-Marańda,
- Sebastian Giebel,
- Wiesław Wiktor Jędrzejczak
Affiliations
- Marta Libura
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Karolina Karabin
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Paweł Tyrna
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Anna Czyż
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wrocław, 50-137 Wrocław, Poland
- Hanna Makuch-Łasica
- Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
- Bożena Jaźwiec
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wrocław, 50-137 Wrocław, Poland
- Monika Paluszewska
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Beata Piątkowska-Jakubas
- Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland
- Magdalena Zawada
- Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland
- Michał Gniot
- Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, 61-701 Poznań, Poland
- Joanna Trubicka
- Children’s Memorial Health Institute, 04-736 Warsaw, Poland
- Magdalena Szymańska
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Katarzyna Borg
- Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
- Marta Więsik
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Sylwia Czekalska
- Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland
- Izabela Florek
- Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland
- Maria Król
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Małgorzata Paszkowska-Kowalewska
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Lidia Gil
- Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, 61-701 Poznań, Poland
- Katarzyna Kapelko-Słowik
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wrocław, 50-137 Wrocław, Poland
- Elżbieta Patkowska
- Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
- Agnieszka Tomaszewska
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Krzysztof Mądry
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Rafał Machowicz
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Tomasz Czerw
- Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland
- Agnieszka Piekarska
- Department of Hematology and Transplantology, Medical University of Gdańsk, 80-214 Gdańsk, Poland
- Magdalena Dutka
- Department of Hematology and Transplantology, Medical University of Gdańsk, 80-214 Gdańsk, Poland
- Anna Kopińska
- Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, 40-032 Katowice, Poland
- Grzegorz Helbig
- Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, 40-032 Katowice, Poland
- Tomasz Gromek
- Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland
- Krzysztof Lewandowski
- Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, 61-701 Poznań, Poland
- Marta Zacharczuk
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wrocław, 50-137 Wrocław, Poland
- Anna Pastwińska
- Department of Tumor Biology and Genetics, Medical University of Warsaw, 02-106 Warsaw, Poland
- Tomasz Wróbel
- Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wrocław, 50-137 Wrocław, Poland
- Olga Haus
- Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
- Grzegorz Basak
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Jerzy Hołowiecki
- Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland
- Przemysław Juszczyński
- Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
- Ewa Lech-Marańda
- Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
- Sebastian Giebel
- Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland
- Wiesław Wiktor Jędrzejczak
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- DOI
- https://doi.org/10.3390/cancers15225431
- Journal volume & issue
-
Vol. 15,
no. 22
p. 5431
Abstract
Adult acute lymphoblastic leukemia (ALL) is associated with poor outcomes. ALL is initiated by primary aberrations, but secondary genetic lesions are necessary for overt ALL. In this study, we reassessed the value of primary and secondary aberrations in intensively treated ALL patients in relation to mutator enzyme expression. RT-PCR, genomic PCR, and sequencing were applied to evaluate primary aberrations, while qPCR was used to measure the expression of RAG and AID mutator enzymes in 166 adult ALL patients. Secondary copy number alterations (CNA) were studied in 94 cases by MLPA assay. Primary aberrations alone stratified 30% of the patients (27% high-risk, 3% low-risk cases). The remaining 70% intermediate-risk patients included BCR::ABL1pos subgroup and ALL lacking identified genetic markers (NEG ALL). We identified three CNA profiles: high-risk bad-CNA (CNAhigh/IKZF1pos), low-risk good-CNA (all other CNAs), and intermediate-risk CNAneg. Furthermore, based on RAG/AID expression, we report possible mechanisms underlying the CNA profiles associated with poor outcome: AID stratified outcome in CNAneg, which accompanied most likely a particular profile of single nucleotide variations, while RAG in CNApos increased the odds for CNAhigh/IKZF1pos development. Finally, we integrated primary genetic aberrations with CNA to propose a revised risk stratification code, which allowed us to stratify 75% of BCR::ABL1pos and NEG patients.
Keywords
