Sökning: id:"swepub:oai:lup.lub.lu.se:3f3304bc-46dc-4f0c-b8a6-b53bd9bb593e" >
NOTCH1 mutations in...
NOTCH1 mutations influence survival in chronic lymphocytic leukemia patients
-
- Willander, Kerstin (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet,Hematologiska kliniken US
-
- Kumar Dutta, Ravi (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet
-
- Ungerbäck, Jonas (författare)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Hälsouniversitetet
-
visa fler...
-
- Gunnarsson, Rebeqa (författare)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lund University, Sweden
-
- Juliusson, Gunnar (författare)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lund University, Sweden
-
- Fredrikson, Mats (författare)
- Linköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet
-
- Linderholm, Mats (författare)
- Stockholms Sjukhem, Sweden
-
- Söderkvist, Peter (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet
-
visa färre...
-
(creator_code:org_t)
- 2013-06-04
- 2013
- Engelska.
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13
- Relaterad länk:
-
https://portal.resea... (primary) (free)
-
visa fler...
-
http://dx.doi.org/10... (free)
-
https://bmccancer.bi...
-
https://doi.org/10.1...
-
https://liu.diva-por... (primary) (Raw object)
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
visa färre...
Abstract
Ämnesord
Stäng
- Background: NOTCH1 PEST domain mutations in chronic lymphocytic leukemia have recently been shown to be of prognostic relevance. Both NOTCH1 and NOTCH2 are constitutively activated in B-cell CLL but not expressed in normal B cells and may be involved in survival and resistance to apoptosis in CLL. We screened for mutations in different parts of both NOTCH1 and NOTCH2 genes and related the changes to survival and other known risk factors. Methods: In a cohort of 209 CLL patients, we used single strand conformation analysis to determine which of the samples carrying the NOTCH mutations and direct dideoxy sequencing was used to determine the exact nucleotide changes. Kaplan-Meier curves and log rank test were used to determine overall survival for NOTCH1 mutated cases and Cox regression analysis was used to calculate hazardous ratios. Results: In the present study, we found NOTCH1 PEST domain mutations in 6.7% of the cases. A shorter overall survival was found in patients with NOTCH1 mutations compared to wildtype (p = 0.049). Further, we also examined the extracellular and the heterodimerisation domains of the NOTCH1 gene and the PEST domain and heterodimerisation domain of the NOTCH2 gene, but no mutations were found in these regions. NOTCH1 mutations were most commonly observed in patients with unmutated IGHV gene (10/14), and associated with a more aggressive disease course. In addition, NOTCH1 mutations were almost mutually exclusive with TP53 mutations. In the combined group of NOTCH1 (6.7%) or TP53 (6.2%) mutations, a significant difference in overall survival compared to the wildtype NOTCH1 and TP53 was found (p = 0.002). Conclusions: Both NOTCH1 and TP53 mutations seem to be independent predictive markers for worse outcome in CLL-patients and this study emphasizes the contention that NOTCH1 mutations is a novel risk marker.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Chronic lymphocytic leukemia
- NOTCH1 mutations
- TP53 mutations
- Prognostic markers
- Chronic lymphocytic leukemia; NOTCH1 mutations; TP53 mutations; Prognostic markers
- MEDICINE
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas