Telomere status in chronic lymphocytic leukemia with TP53 disruption Article Swipe
Romain Guièze
,
Mélanie Pagès
,
Lauren Véronèse
,
Patricia Combes
,
Richard Lemal
,
Mathilde Gay‐Bellile
,
Martine Chauvet
,
Mary Callanan
,
Fabrice Kwiatkowski
,
Bruno Pereira
,
Philippe Vago
,
Jacques‐Olivier Bay
,
Olivier Tournilhac
,
Andréï Tchirkov
·
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.18632/oncotarget.10927
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.18632/oncotarget.10927
In chronic lymphocytic leukemia (CLL), telomere dysfunction is associated with poor outcomes. TP53 is involved in cellular responses to dysfunctional telomeres, and its inactivation is the strongest adverse prognostic factor for CLL. Given the biological relationship between TP53 and telomeres, and their prognostic value, it is important to improve our understanding of the impact of TP53 alterations on telomeres. We performed a comprehensive study of the deletions and mutations of the TP53 gene and telomere parameters, including hTERT and the shelterin complex, in 115 CLL patients. We found that any type of TP53 alteration was associated with very short telomeres and high hTERT expression, independently of other biological CLL features. Patients with disrupted TP53 showed telomere deletions and chromosomal end-to-end fusions in cells with complex karyotypes. TP53 disruption was characterized by downregulation of shelterin genes. Interestingly, low expression of POT1, TPP1 and TIN2 was also found in some patients with wild-type TP53 and had an adverse impact on progression-free survival after standard genotoxic therapy. In conclusion, we have demonstrated that patients with disrupted TP53 have severe telomere dysfunction and high genomic instability. Thus, the telomeric profile could be tested as a biomarker in CLL patients treated with new therapeutic agents.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.18632/oncotarget.10927
- http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=10927&path%5B%5D=34601
- OA Status
- diamond
- Cited By
- 20
- References
- 35
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2486588543
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2486588543Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.18632/oncotarget.10927Digital Object Identifier
- Title
-
Telomere status in chronic lymphocytic leukemia with TP53 disruptionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2016Year of publication
- Publication date
-
2016-07-29Full publication date if available
- Authors
-
Romain Guièze, Mélanie Pagès, Lauren Véronèse, Patricia Combes, Richard Lemal, Mathilde Gay‐Bellile, Martine Chauvet, Mary Callanan, Fabrice Kwiatkowski, Bruno Pereira, Philippe Vago, Jacques‐Olivier Bay, Olivier Tournilhac, Andréï TchirkovList of authors in order
- Landing page
-
https://doi.org/10.18632/oncotarget.10927Publisher landing page
- PDF URL
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https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=10927&path%5B%5D=34601Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
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-
diamondOpen access status per OpenAlex
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https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=10927&path%5B%5D=34601Direct OA link when available
- Concepts
-
Chronic lymphocytic leukemia, Telomere, Medicine, Leukemia, Immunology, Cancer research, Oncology, Biology, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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20Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1, 2022: 4, 2021: 4, 2020: 4, 2019: 3Per-year citation counts (last 5 years)
- References (count)
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35Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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