title: Loss of TRIM62 expression is an independent adverse prognostic factor in acute myeloid leukemia.
abstract: BACKGROUND
  Tripartite motif (TRIM)-62 is a putative tumor suppressor gene whose role in leukemia is unknown.
  
  
  METHODS
  We evaluated the effect of TRIM62 protein expression in patients with acute myeloid leukemia (AML). We used reverse-phase protein array methodology to determine TRIM62 levels in leukemia-enriched protein samples from 511 patients newly diagnosed with AML.
  
  
  RESULTS
  TRIM62 levels in AML cells were significantly lower than in normal CD34-positive cells, suggesting that TRIM62 loss might be involved in leukemogenesis, but was not associated with specific karyotypic abnormalities or Nucleophosmin (NPM1), Fms-like Tyrosine Kinase-3 (FLT3), or rat sarcoma viral oncogene (RAS) mutational status. Low TRIM62 levels were associated with shorter complete remission duration and significantly shorter event-free and overall survival rates, particularly among patients with intermediate-risk cytogenetics. In that AML subgroup, age and TRIM62 levels were the most powerful independent prognostic factors for survival. TRIM62 protein levels further refined the risk associated with NPM1 and FLT3 mutational status. TRIM62 loss was associated with altered expression of proteins involved in leukemia stem cell homeostasis (β-catenin and Notch), cell motility, and adhesion (integrin-β3, ras-related C3 botulinum toxin substrate [RAC], and fibronectin), hypoxia (Hypoxia-inducible factor 1-alpha [HIF1α], egl-9 family hypoxia-inducible factor 1 [Egln1], and glucose-regulated protein, 78 kDa [GRP78]), and apoptosis (B-cell lymphoma-extra large (BclXL) and caspase 9).
  
  
  CONCLUSIONS
  Low TRIM62 levels, consistent with a tumor suppressor role, represent an independent adverse prognostic factor in AML.
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.affiliation: Department of Bioinformatics, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Nianxiang
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Yi Hua
authors.initials: YH
authors.lastname: Qiu
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Sean
authors.initials: S
authors.lastname: Post
authors.affiliation: Dan L. Duncan Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, TX.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Bioinformatics, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kornblau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D040901:Proteomics; D015996:Survival Rate; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D055815:Young Adult
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000716967:NPM1 protein, human; D000070584:Tripartite Motif Proteins; D000090243:Nucleophosmin; C583162:TRIM62 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: AML; Proteomics; RPPA; Reverse phase protein array; TRIM62