Differential prognosis of single and multiple TP53 abnormalities in high-count MBL and untreated CLL Article Swipe
Rosalie Griffin
,
Julia E. Wiedmeier
,
Sameer A. Parikh
,
Chantal E. McCabe
,
Daniel R. O’Brien
,
Nicholas J. Boddicker
,
Geffen Kleinstern
,
Kari G. Rabe
,
Laura A. Bruins
,
Sochilt Brown
,
Cecília Bonolo de Campos
,
Wei Ding
,
José F. Leis
,
Paul J. Hampel
,
Timothy G. Call
,
Daniel L. Van Dyke
,
Neil E. Kay
,
James R. Cerhan
,
Huihuang Yan
,
Susan L. Slager
,
Esteban Braggio
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2022009040
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2022009040
TP53 aberrations, including mutations and deletion of 17p13, are important adverse prognostic markers in chronic lymphocytic leukemia (CLL) but are less studied in high count monoclonal B-cell lymphocytosis (HCMBL), an asymptomatic pre-malignant stage of CLL. Here we estimated the prevalence and impact of TP53 aberrations in 1,230 newly diagnosed treatment-naïve individuals (849 CLL, 381 HCMBL). We defined TP53 state as: wild-type (no TP53 mutations and normal 17p), single-hit (del(17p) or one TP53 mutation), or multi-hit (TP53 mutation and del(17p), TP53 mutation and loss of heterozygosity, or multiple TP53 mutations). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time to first treatment and overall survival by TP53 state. We found 64 (7.5%) CLL patients and 17 (4.5%) HCMBL individuals had TP53 mutations with variant allele fraction >10%. Del(17p) was present in 58 (6.8%) of CLL and 11 (2.9%) of HCMBL cases. Most individuals had wild-type (N=1,128, 91.7%) TP53 state, followed by multi-hit (N=55, 4.5%) and then single-hit (N=47, 3.8%) TP53 state. The risk of shorter time to therapy and death increased with the number of TP53 abnormalities. Compared to wild-type patients, multi-hit patients had 3-fold and single-hit patients had 1.5-fold increased risk of requiring therapy. Multi-hit patients also had 2.9-fold increased risk of death compared to wild-type. These results remained stable after accounting for other known poor prognostic factors. Both TP53 mutations and del(17p) may provide important prognostic information for HCMBL and CLL that would be missed if only one were measured.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1182/bloodadvances.2022009040
- https://ashpublications.org/bloodadvances/article-pdf/7/13/3169/2062845/blooda_adv-2022-009040-main.pdf
- OA Status
- gold
- Cited By
- 15
- References
- 34
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4323295039
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4323295039Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1182/bloodadvances.2022009040Digital Object Identifier
- Title
-
Differential prognosis of single and multiple TP53 abnormalities in high-count MBL and untreated CLLWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-03-06Full publication date if available
- Authors
-
Rosalie Griffin, Julia E. Wiedmeier, Sameer A. Parikh, Chantal E. McCabe, Daniel R. O’Brien, Nicholas J. Boddicker, Geffen Kleinstern, Kari G. Rabe, Laura A. Bruins, Sochilt Brown, Cecília Bonolo de Campos, Wei Ding, José F. Leis, Paul J. Hampel, Timothy G. Call, Daniel L. Van Dyke, Neil E. Kay, James R. Cerhan, Huihuang Yan, Susan L. Slager, Esteban BraggioList of authors in order
- Landing page
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https://doi.org/10.1182/bloodadvances.2022009040Publisher landing page
- PDF URL
-
https://ashpublications.org/bloodadvances/article-pdf/7/13/3169/2062845/blooda_adv-2022-009040-main.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://ashpublications.org/bloodadvances/article-pdf/7/13/3169/2062845/blooda_adv-2022-009040-main.pdfDirect OA link when available
- Concepts
-
Chronic lymphocytic leukemia, Hazard ratio, Internal medicine, Medicine, Asymptomatic, Proportional hazards model, Lymphocytosis, Loss of heterozygosity, Gastroenterology, Leukemia, Confidence interval, Oncology, Immunology, Biology, Allele, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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15Total citation count in OpenAlex
- Citations by year (recent)
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2025: 5, 2024: 8, 2023: 2Per-year citation counts (last 5 years)
- References (count)
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34Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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