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TP 53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis
Author(s) -
Loghavi Sanam,
AlIbraheemi Alyaa,
Zuo Zhuang,
GarciaManero Guillermo,
Yabe Mariko,
Wang Sa A.,
Kantarjian Hagop M.,
Yin Cameron C.,
Miranda Roberto N.,
Luthra Raja,
Medeiros L. Jeffrey,
BuesoRamos Carlos E.,
Khoury Joseph D.
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13529
Subject(s) - myelodysplastic syndromes , cd34 , international prognostic scoring system , bone marrow , medicine , immunohistochemistry , fibrosis , mutation , sanger sequencing , cancer research , oncology , pathology , biology , stem cell , gene , genetics
Summary Bone marrow ( BM ) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes ( MDS ). TP 53 mutations and TP 53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP 53 mutations and TP 53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis ( MDS ‐F). Expression of TP 53 was evaluated in BM core biopsy specimens using dual‐colour CD 34/ TP 53 immunohistochemistry with computer‐assisted image analysis. Mutation analysis was performed using next‐generation sequencing, or Sanger sequencing methods. TP 53 mutations were present in 47·1% of cases. TP 53 mutation was significantly associated with TP 53 expression ( P = 0·0294). High levels of TP 53 expression (3 + in ≥10% cells) were associated with higher BM blast counts ( P = 0·0149); alterations of chromosomes 5 ( P = 0·0009) or 7 ( P = 0·0141); complex karyotype ( P = 0·0002); high‐ and very‐high risk IPSS ‐R groups ( P = 0·009); and TP 53 mutations ( P = 0·0003). High TP 53 expression independently predicted shorter overall survival ( OS ) by multivariate analysis ( P = <0·001). Expression of TP 53 by CD 34‐positive cells was associated with shorter OS and leukaemia‐free survival ( P = 0·0428). TP 53 overexpression is a predictor of poor outcome in patients with MDS ‐F.