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dc.contributor.author Saft L
dc.contributor.author Karimi M
dc.contributor.author Ghaderi M
dc.contributor.author Matolcsy, András
dc.contributor.author Mufti GJ
dc.contributor.author Kulasekararaj A
dc.contributor.author Gohring G
dc.contributor.author Giagounidis A
dc.contributor.author Selleslag D
dc.contributor.author Muus P
dc.contributor.author Sanz G
dc.contributor.author Mittelman M
dc.contributor.author Bowen D
dc.contributor.author Porwit A
dc.contributor.author Fu T
dc.contributor.author Backstrom J
dc.contributor.author Fenaux P
dc.contributor.author MacBeth KJ
dc.contributor.author Hellstrom-Lindberg E
dc.date.accessioned 2016-06-29T13:44:56Z
dc.date.available 2016-06-29T13:44:56Z
dc.date.issued 2014
dc.identifier 84901712631
dc.identifier.citation pagination=1041-1049; journalVolume=99; journalIssueNumber=6; journalTitle=HAEMATOLOGICA;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/2966
dc.identifier.uri doi:10.3324/haematol.2013.098103
dc.description.abstract Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring System as low- or intermediate-1-risk (lower-risk) are considered to have an indolent course; however, recent data have identified a subgroup of these patients with more aggressive disease and poorer outcomes. Using deep sequencing technology, we previously demonstrated that 18% of patients with lower-risk del(5q) myelodysplastic syndromes carry TP53 mutated subclones rendering them at higher risk of progression. In this study, bone marrow biopsies from 85 patients treated with lenalidomide in the MDS-004 clinical trial were retrospectively assessed for p53 expression by immunohistochemistry in association with outcome. Strong p53 expression in >/= 1% of bone marrow progenitor cells, observed in 35% (30 of 85) of patients, was significantly associated with higher acute myeloid leukemia risk (P=0.0006), shorter overall survival (P=0.0175), and a lower cytogenetic response rate (P=0.009), but not with achievement or duration of 26-week transfusion independence response. In a multivariate analysis, p53-positive immunohistochemistry was the strongest independent predictor of transformation to acute myeloid leukemia (P=0.0035). Pyrosequencing analysis of laser-microdissected cells with strong p53 expression confirmed the TP53 mutation, whereas cells with moderate expression predominantly had wild-type p53. This study validates p53 immunohistochemistry as a strong and clinically useful predictive tool in patients with lower-risk del(5q) myelodysplastic syndromes. This study was based on data from the MDS 004 trial (clinicaltrials.gov identifier: NCT00179621).
dc.relation.ispartof urn:issn:0390-6078
dc.title p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q).
dc.type Journal Article
dc.date.updated 2015-12-07T14:41:08Z
dc.language.rfc3066 en
dc.identifier.mtmt 2747668
dc.identifier.wos 000342832100020
dc.identifier.pubmed 24682512
dc.contributor.department SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet
dc.contributor.institution Semmelweis Egyetem


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