Search: WFRF:(Rosenquist Richard)
> (2020-2024) >
The Number of Signa...
The Number of Signaling Pathways Altered by Driver Mutations in Chronic Lymphocytic Leukemia Impacts Disease Outcome
-
- Brieghel, Christian (author)
- Rigshosp, Dept Hematol, Copenhagen, Denmark.
-
- da Cunha-Bang, Caspar (author)
- Rigshosp, Dept Hematol, Copenhagen, Denmark.
-
- Yde, Christina Westmose (author)
- Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
-
show more...
-
- Schmidt, Ane Yde (author)
- Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
-
Kinalis, Savvas (author)
-
- Nadeu, Ferran (author)
- Inst Invest Biomed August Pi & Sunyer IDIBAPS, Lymphoid Neoplasms Program, Barcelona, Spain.;Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain.
-
- Andersen, Michael Asger (author)
- Rigshosp, Dept Hematol, Copenhagen, Denmark.
-
- Jacobsen, Line Offenbach (author)
- Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
-
- Andersen, Mette Klarskov (author)
- Rigshosp, Dept Clin Genet, Copenhagen, Denmark.
-
- Pedersen, Lone Bredo (author)
- Rigshosp, Dept Hematol, Copenhagen, Denmark.
-
- Delgado, Julio (author)
- Inst Invest Biomed August Pi & Sunyer IDIBAPS, Lymphoid Neoplasms Program, Barcelona, Spain.;Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain.;Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain.
-
- Baumann, Tycho (author)
- Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain.
-
- Mattsson, Mattias (author)
- Uppsala universitet,Hematologi,Experimentell och klinisk onkologi
-
- Mansouri, Larry (author)
- Karolinska Institutet
-
- Rosenquist, Richard (author)
- Karolinska Institutet
-
- Campo, Elias (author)
- Inst Invest Biomed August Pi & Sunyer IDIBAPS, Lymphoid Neoplasms Program, Barcelona, Spain.;Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain.;Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain.;Univ Barcelona, Barcelona, Spain.
-
- Nielsen, Finn Cilius (author)
- Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
-
- Niemann, Carsten Utoft (author)
- Rigshosp, Dept Hematol, Copenhagen, Denmark.
-
show less...
-
Rigshosp, Dept Hematol, Copenhagen, Denmark Rigshosp, Ctr Genom Med, Copenhagen, Denmark. (creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2020
- 2020
- English.
-
In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 26:6, s. 1507-1515
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- Purpose: Investigation of signaling pathways altered by recurrent gene mutations and their clinical impact in a consecutive cohort of patients with newly diagnosed chronic lymphocytic leukemia (CLL). The heterogeneous clinical course and genetic complexity of CLL warrant improved molecular prognostication. However, the prognostic value of recurrent mutations at the time of diagnosis remains unclear. Experimental Design: We sequenced samples from 314 consecutive, newly diagnosed patients with CLL to investigate the clinical impact of 56 recurrently mutated genes assessed by next-generation sequencing. Results: Mutations were identified in 70% of patients with enrichment among IGHV unmutated cases. With 6.5 years of follow-up, 15 mutated genes investigated at the time of diagnosis demonstrated significant impact on time to first treatment (TTFT). Carrying driver mutations was associated with shorter TTFT and poor overall survival. For outcome from CLL diagnosis, the number of signaling pathways altered by driver mutations stratified patients better than the number of driver mutations. Moreover, we demonstrated gradual impact on TTFT with increasing number of altered pathways independent of CLL-IPI risk. Thus, a 25-gene, pathway-based biomarker assessing recurrent mutations refines prognostication in CLL, in particular for CLL-IPI low- and intermediate-risk patients. External validation emphasized that a broad gene panel including low burden mutations was key for the biomarker based on altered pathways. Conclusions: We propose to include the number of pathways altered by driver mutations as a biomarker together with CLL-IPI in prospective studies of CLL from time of diagnosis for incorporation into clinical care and personalized follow-up and treatment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Brieghel, Christ ...
-
da Cunha-Bang, C ...
-
Yde, Christina W ...
-
Schmidt, Ane Yde
-
Kinalis, Savvas
-
Nadeu, Ferran
-
show more...
-
Andersen, Michae ...
-
Jacobsen, Line O ...
-
Andersen, Mette ...
-
Pedersen, Lone B ...
-
Delgado, Julio
-
Baumann, Tycho
-
Mattsson, Mattia ...
-
Mansouri, Larry
-
Rosenquist, Rich ...
-
Campo, Elias
-
Nielsen, Finn Ci ...
-
Niemann, Carsten ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Hematology
- Articles in the publication
-
Clinical Cancer ...
- By the university
-
Uppsala University
-
Karolinska Institutet