title: TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis.
abstract: Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 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 TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 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 TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = <0·001). Expression of TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F.
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sanam
authors.identifier: http://orcid.org/0000-0001-8980-3202
authors.initials: S
authors.lastname: Loghavi
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alyaa
authors.initials: A
authors.lastname: Al-Ibraheemi
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mariko
authors.initials: M
authors.lastname: Yabe
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Cameron C
authors.initials: CC
authors.lastname: Yin
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Khoury
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D012155:Reticulin; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012155:Reticulin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: TP53; TP53 expression; fibrosis; myelodysplastic syndrome; next-generation sequencing