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 |