title: Prognostic importance of histone methyltransferase MLL5 expression in acute myeloid leukemia.
abstract: OBJECTIVE
  To assess the prognostic importance of mixed lineage leukemia 5 (MLL5) expression in acute myeloid leukemia (AML).
  
  
  METHODS
  MLL5 transcript levels from 509 patients with AML who were treated in multicenter trials AML SHG 0199 and AML SHG 0295 and 48 healthy volunteers were analyzed by real-time reverse-transcription polymerase chain reaction in the context of other molecular markers (NPM1, FLT3, CEBPA, IDH1/IDH2, NRAS, KIT, MN1, BAALC, ERG, and WT1).
  
  
  RESULTS
  Patients with high (n = 127) compared with low (n = 382) MLL5 expression had a higher complete response rate in multivariate analysis (odds ratio, 1.87; 95% CI, 1.08 to 3.24; P = .026). In multivariate analysis, high MLL5 expression was a favorable prognostic marker for overall survival (OS; hazard ratio [HR], 0.66; 95% CI, 0.49 to 0.89; P = .007) and relapse-free survival (RFS; HR, 0.72; 95% CI, 0.52 to 1.01; P = .057). Patient characteristics, cytogenetic aberrations, and gene mutations were similarly distributed between patients with high and low MLL5 expression except for a higher platelet count in those with high MLL5 expression. MLL5 expression independently predicted prognosis in cytogenetically normal AML patients (n = 268; OS: HR, 0.53; 95% CI, 0.33 to 086; P = .011; RFS: HR, 0.61; 95% CI, 0.38 to 0.99; P = .05) and in patients with core-binding factor leukemias (n = 81; OS: HR, 0.12; 95% CI, 0.02 to 0.91; P = .04; RFS: HR, 0.18; 95% CI, 0.04 to 0.77; P = .02). The prognostic importance of high MLL5 expression was independently validated in 167 patients treated in the AMLSG 07/04 trial (OS: HR, 0.5; 95% CI, 0.27 to 0.92; P = .023; RFS: HR, 0.49; 95% CI, 0.25 to 0.96; P = .033).
  
  
  CONCLUSIONS
  High MLL5 expression levels are associated with a favorable outcome and may improve risk and treatment stratification in AML.
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Str 1, 30625 Hannover, Germany. damm.frederik@mh-hannover.de
authors.forename: Frederik
authors.initials: F
authors.lastname: Damm
authors.forename: Tina
authors.initials: T
authors.lastname: Oberacker
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.forename: Ewa
authors.initials: E
authors.lastname: Surdziel
authors.forename: Katharina
authors.initials: K
authors.lastname: Wagner
authors.forename: Anuhar
authors.initials: A
authors.lastname: Chaturvedi
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.forename: Karoline
authors.initials: K
authors.lastname: Bomm
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heil
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D000090243:Nucleophosmin; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C460660:KMT2E protein, human; C000716967:NPM1 protein, human; D000090243:Nucleophosmin