Abstract
Background
Next-generation sequencing (NGS) is an emerging technology that can comprehensively assess the diversity of the immune system. We explored the feasibility of NGS in detecting minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) based on immunoglobulin and T cell receptor.
Methods
Bone marrow samples were collected pre- and post-treatment with pediatric ALL admitted to Shenzhen Children's Hospital from February 1st, 2020 to January 31st, 2021. We analyzed the MRD detected by NGS, multiparametric flow cytometry (MFC) and real-time quantitative PCR (RQ–PCR), and analyzed risk factors of positive NGS–MRD at the end of B-ALL induction chemotherapy.
Results
A total of paired 236 bone marrow samples were collected from 64 children with ALL (58 B-ALL and 6 T-ALL). The decrease in the clonal rearrangement frequency of IGH, IGK, and IGL was generally consistent after treatment. Positive MRD was detected in 57.5% (77/134) of B-ALL and 80% (12/15) of T-ALL by NGS after chemotherapy, which was higher than those detected by MFC and RQ–PCR. In B-ALL patients, MRD results detected by NGS were consistent with MFC (r = 0.708, p < 0.001) and RQ–PCR (r = 0.618, p < 0.001). At the end of induction, NGS–MRD of 40.4% B-ALL was > 0.01% and multivariate analysis indicated that ≧2 clonal rearrangement sequences before treatment were an independent factor of negative NGS–MRD.
Conclusions
NGS is more sensitive than MFC and RQ–PCR for MRD measurement. B-ALL children with ≧2 clonal rearrangements detected by NGS before treatment are difficult to switch to negative MRD after chemotherapy.
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Data availability
The data that support the findings of this study are available on request from the corresponding author.
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Acknowledgements
We are grateful to all the colleagues in Hematology and Oncology department of Shenzhen Children's Hospital for supporting this work in the clinical practice. We thank Mingfeng Bai and Cheng Chen from Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences for revising the manuscript. This project was supported by Sanming Project of Medicine in Shenzhen (SZSM201512033), Guangdong Medical Science and Technology Research Project (A2020101), Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP012), Shenzhen Key Medical Discipline Construction Fund (SZXK034), and Shenzhen Healthcare Research Project (SZLY2018015).
Funding
This work was supported by Sanming Project of Medicine in Shenzhen (SZSM201512033), Guangdong Medical Science and Technology Research Project (A2020101), Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP012), Shenzhen Key Medical Discipline Construction Fund (SZXK034), and Shenzhen Healthcare Research Project (SZLY2018015).
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(I) conception and design: Huirong Mai, Qin Li, Sixi Liu (II) Administrative support: Sixi Liu; (III) Provision of study material or patients: Guobing Wang, Ying Wang, Shilin Liu, Xue Tang, Fen Chen; (IV) Collection and assembly of data: Guichi Zhou, Yi Liu, Tonghui Li, Lulu Wang, Chunyan Wang, Feiqiu Wen; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Shenzhen Children's Hospital (June 11, 2021/No. 202105102).
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Mai, H., Li, Q., Wang, G. et al. Clinical application of next-generation sequencing-based monitoring of minimal residual disease in childhood acute lymphoblastic leukemia. J Cancer Res Clin Oncol 149, 3259–3266 (2023). https://doi.org/10.1007/s00432-022-04151-6
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DOI: https://doi.org/10.1007/s00432-022-04151-6