التفاصيل البيبلوغرافية
| العنوان: |
Clonal dynamics in pediatric B-cell precursor acute lymphoblastic leukemia with very early relapse |
| المؤلفون: |
Antić, Željko, Yu, Jiangyan, Bornhauser, Beat C, Lelieveld, Stefan H, van der Ham, Cedric G, van Reijmersdal, Simon V, Morgado, Lionel, Elitzur, Sarah, Bourquin, Jean-Pierre, Cazzaniga, Giovanni, Eckert, Cornelia, Camós, Mireia, Sutton, Rosemary, Cavé, Hélène, Moorman, Anthony V, Sonneveld, Edwin, Geurts van Kessel, Ad, van Leeuwen, Frank N, Hoogerbrugge, Peter M, Waanders, Esmé, Kuiper, Roland P |
| المساهمون: |
PMC Medisch specialisten, Genetica Sectie Genoomdiagnostiek |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
clonal dynamics, pediatric acute lymphoblastic leukemia, RAD21, TP53, very early relapse, WHSC1, Hematology, Oncology, Pediatrics, Perinatology, and Child Health, Research Support, Non-U.S. Gov't, Journal Article |
| الوصف: |
INTRODUCTION: One-quarter of the relapses in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occur very early (within 18 months, before completion of treatment), and prognosis in these patients is worse compared to cases that relapse after treatment has ended. METHODS: In this study, we performed a genomic analysis of diagnosis-relapse pairs of 12 children who relapsed very early, followed by a deep-sequencing validation of all identified mutations. In addition, we included one case with a good initial treatment response and on-treatment relapse at the end of upfront therapy. RESULTS: We observed a dynamic clonal evolution in all cases, with relapse almost exclusively originating from a subclone at diagnosis. We identified several driver mutations that may have influenced the outgrowth of a minor clone at diagnosis to become the major clone at relapse. For example, a minimal residual disease (MRD)-based standard-risk patient with ETV6-RUNX1-positive leukemia developed a relapse from a TP53-mutated subclone after loss of the wildtype allele. Furthermore, two patients with TCF3-PBX1-positive leukemia that developed a very early relapse carried E1099K WHSC1 mutations at diagnosis, a hotspot mutation that was recurrently encountered in other very early TCF3-PBX1-positive leukemia relapses as well. In addition to alterations in known relapse drivers, we found two cases with truncating mutations in the cohesin gene RAD21. CONCLUSION: Comprehensive genomic characterization of diagnosis-relapse pairs shows that very early relapses in BCP-ALL frequently arise from minor subclones at diagnosis. A detailed understanding of the therapeutic pressure driving these events may aid the development of improved therapies. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
1545-5009 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/444995Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/444995Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.EDD229BC |
| قاعدة البيانات: |
BASE |
