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Results of Polish Adult Leukemia Study Group (PALG) project assessing TP53 mutations with next-generation sequencing technology in relapsed and refractory chronic lymphocytic leukemia patients — an 18-month update
Affiliations- Department of Tumor Biology and Genetics, Medical University of Warsaw, Warsaw, Poland
- Postgraduate School of Molecular Medicine, Warsaw, Poland
- Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
- Specialist Oncological Hospital Nu-Med, Czestochowa, Poland
- Regional Hospital, Suwalki, Poland
- Masovian Specialist Hospital, Radom, Poland
- Municipal Hospital, Chorzow, Poland
- Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland
- Oncology Specialist Hospital, Brzozow, Poland
- Department of Hematology and Bone Marrow Transplantation, Katowice Medical Department, Silesian Medical University, Katowice, Poland
- Department of Hematology, Transplantation and Internal Medicine, Medical University, Warsaw, Poland
- Department of Internal Medicine and Hematology, Military Institute of Medicine, Warsaw, Poland
- Department of Hematology, Specialist District Hospital, Rzeszow, Poland
- Department of Hematology, Specialist District Hospital, Rzeszow, Poland
- Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland
- Department of Hematology, Copernicus Hospital, Torun, Poland
- Medical University of Bialystok, Bialystok, Poland
- Rydygier Specialist Hospital, Krakow, Poland
- Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
- Department of Tumor Biology and Genetics, Medical University of Warsaw, Warsawa, Poland
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Abstract
Indtroduction and methods: In chronic lymphocytic leukemia (CLL), molecular and cytogenetic diagnostics are crucial for the determination of accurate prognosis and treatment choice. Among different genetic aberrations, del(17p13) or TP53 mutations constitute high-risk factors, and early identification of such defects is a high priority for CLL patients. While cytogenetic diagnostics is well-established and accessible for the majority of CLL patients in Poland, molecular diagnostics of TP53 mutations is performed only in a few ERIC-certified centers (eight as of September 2020), and only two of these employ next-generation sequencing (NGS) for routine analysis of TP53 status in CLL patients. Here we report the interim results of a project assessing TP53 mutations with NGS technology in relapsed or refractory CLL patients with confirmed negative del(17p13) status. 249 patients from 32 clinical centers were included in the study. Results: NGS analysis revealed TP53 mutations in 42/249 (17%) patients, half of whom (21/249, 8.5%) had subclonal mutations (VAF ≤10%). These results are in line with published data in relapsed/refractory CLL patients. Conclusions: The results of the project demonstrated the feasibility and accuracy of NGS testing in CLL patients despite several initial logistical and technical obstacles. Our study also proved that, with appropriate funding, CLL patients from any hematological center in Poland can have access to state-of-the-art molecular diagnostics
Abstract
Indtroduction and methods: In chronic lymphocytic leukemia (CLL), molecular and cytogenetic diagnostics are crucial for the determination of accurate prognosis and treatment choice. Among different genetic aberrations, del(17p13) or TP53 mutations constitute high-risk factors, and early identification of such defects is a high priority for CLL patients. While cytogenetic diagnostics is well-established and accessible for the majority of CLL patients in Poland, molecular diagnostics of TP53 mutations is performed only in a few ERIC-certified centers (eight as of September 2020), and only two of these employ next-generation sequencing (NGS) for routine analysis of TP53 status in CLL patients. Here we report the interim results of a project assessing TP53 mutations with NGS technology in relapsed or refractory CLL patients with confirmed negative del(17p13) status. 249 patients from 32 clinical centers were included in the study. Results: NGS analysis revealed TP53 mutations in 42/249 (17%) patients, half of whom (21/249, 8.5%) had subclonal mutations (VAF ≤10%). These results are in line with published data in relapsed/refractory CLL patients. Conclusions: The results of the project demonstrated the feasibility and accuracy of NGS testing in CLL patients despite several initial logistical and technical obstacles. Our study also proved that, with appropriate funding, CLL patients from any hematological center in Poland can have access to state-of-the-art molecular diagnostics
Keywords
chronic lymphocytic leukemia, TP53 mutations, next-generation sequencing, targeted sequencing
About this articleTitle
Results of Polish Adult Leukemia Study Group (PALG) project assessing TP53 mutations with next-generation sequencing technology in relapsed and refractory chronic lymphocytic leukemia patients — an 18-month update
Journal
Issue
Article type
Original research article
Pages
94-102
Page views
522
Article views/downloads
343
DOI
10.5603/AHP.2021.0015
Bibliographic record
Acta Haematol Pol 2021;52(2):94-102.
Keywords
chronic lymphocytic leukemia
TP53 mutations
next-generation sequencing
targeted sequencing
Authors
Monika Pepek
Bartosz Pula
Marcin M. Machnicki
Elzbieta Morawiec-Szymonik
Alina Urbanowicz
Iwona Sokolowska-Giezgala
Zofia Spyra-Gorny
Agnieszka Szeremet
Dariusz Kumorek
Ryszard Wichary
Dorota Zdunczyk
Ewa Bodzenta
Kamila Kruczkowska-Tarantowicz
Katarzyna Warzybok
Magdalena Olszewska-Szopa
Jolanta Wieczorek
Marek Dudzinski
Waldemar Tomczak
Dominika Wisniewska-Organek
Pawel Bernatowicz
Anna Labedz
Malgorzata Rydzanicz
Agnieszka Pollak
Rafal Ploski
Tomasz Stoklosa
Krzysztof Jamroziak
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