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Dufour, A.* ; Palermo, G.* ; Zellmeier, E.* ; Mellert, G.* ; Duchateau-Nguyen, G.* ; Schneider, S.* ; Benthaus, T.* ; Kakadia, P.M.* ; Hiddemann, W.* ; Braess, J.* ; Truong, S.* ; Patten, N.* ; Wu, L.* ; Lohmann, S.* ; Dornan, D.* ; GuhaThakurta, D.* ; Yeh, R.F.* ; Salogub, G.* ; Solal-Celigny, P.* ; Dmoszynska, A.* ; Robak, T.* ; Montillo, M.* ; Catalano, J.* ; Geisler, C.H.* ; Weisser, M.* ; Bohlander, S.K.*

Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients.

Blood 121, 3650-3657 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 Article Number: , Supplement: ,
Publisher American Society of Hematology
Reviewing status Peer reviewed
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