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Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients.
Blood 121, 3650-3657 (2013)
In chronic lymphocytic leukemia (CLL) patients, disruptions of the TP53 tumor suppressor pathway by 17p13 deletion (del17p), somatic TP53 mutations, or downregulation of microRNA-34a have been associated with a poor prognosis. So far, the impact of the various TP53 defects has not been evaluated in a large cohort of previously treated and relapsed CLL patients. Here, we present the results of TP53 gene sequencing and fluorescence in situ hybridization for del17p in a phase 3 clinical trial (REACH [Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia]). Of the 457 patients, 52 had TP53 mutations and 37 had del17p. In 24 (46%) of the TP53 mutated patients, no del17p was found and in 9 of the del17p patients, no TP53 mutation was identified. Based on a predicted proportion of TP53 disruption, a complete disruption of TP53 function, either by a combination of point mutations and/or del17p, was associated with a high risk for disease progression. Progression-free survival of patients with a heterozygous TP53 mutation was not significantly different from patients with a completely intact TP53 locus. In addition, only a complete loss of TP53 function correlated with low microRNA-34a expression levels. This trial was registered at www.clinicaltrials.gov as #NCT00090051.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2013
HGF-reported in Year
0
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 121,
Issue: 18,
Pages: 3650-3657
Publisher
American Society of Hematology
Reviewing status
Peer reviewed
Institute(s)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-521000-001
PubMed ID
23525797
Erfassungsdatum
2013-12-06