title: High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children's oncology group.
abstract: Ectopic viral integration site-1 (EVI1) is highly expressed in certain cytogenetic subsets of adult acute myeloid leukaemia (AML), and has been associated with inferior survival. We sought to examine the clinical and biological associations of EVI1(high) , defined as expression in excess of normal controls, in paediatric AML. EVI1 mRNA expression was measured via quantitative real-time polymerase chain reaction in diagnostic specimens obtained from 206 patients. Expression levels were correlated with clinical features and outcome. EVI1(high) was present in 58/206 (28%) patients. MLL rearrangements occurred in 40% of EVI1(high) patients as opposed to 12% of the EVI1(low/absent) patients (P < 0·001). No abnormalities of 3q26 were found in EVI1(high) patients by conventional cytogenetic analysis, nor were cryptic 3q26 abnormalities detected in a subset of patients screened by next-generation sequencing. French-American-British class M7 was enriched in the EVI1(high) group, accounting for 24% of these patients. EVI1(high) patients had significantly lower 5-year overall survival from study entry (51% vs. 68%, P = 0·015). However, in multivariate analysis including other established prognostic markers, EVI1 expression did not retain independent prognostic significance. EVI1 expression is currently being studied in a larger cohort of patients enrolled on subsequent Children's Oncology Group trials, to determine if EVI1(high) has prognostic value in MLL-rearranged or intermediate-risk subsets.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98103, USA. pho@fhcrc.org
authors.forename: Phoenix A
authors.initials: PA
authors.lastname: Ho
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Pollard
authors.forename: Betsy
authors.initials: B
authors.lastname: Hirsch
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Todd
authors.initials: T
authors.lastname: Cooper
authors.forename: Alan S
authors.initials: AS
authors.lastname: Gamis
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D010865:Pilot Projects; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein
keywords: EVI1; MLL; acute myeloid leukaemia; paediatric cancer