title: NUP98-NSD1 fusion in association with FLT3-ITD mutation identifies a prognostically relevant subgroup of pediatric acute myeloid leukemia patients suitable for monitoring by real time quantitative PCR.
abstract: The cytogenetically cryptic t(5;11)(q35;p15) leading to the NUP98-NSD1 fusion is a rare but recurrent gene rearrangement recently reported to identify a group of young AML patients with poor prognosis. We used reverse transcription polymerase chain reaction (PCR) to screen retrospectively diagnostic samples from 54 unselected pediatric AML patients and designed a real time quantitative PCR assay to track individual patient response to treatment. Four positive cases (7%) were identified; three arising de novo and one therapy related AML. All had intermediate risk cytogenetic markers and a concurrent FLT3-ITD but lacked NPM1 and CEBPA mutations. The patients had a poor response to therapy and all proceeded to hematopoietic stem cell transplant. These data lend support to the adoption of screening for NUP98-NSD1 in pediatric AML without otherwise favorable genetic markers. The role of quantitative PCR is also highlighted as a potential tool for managing NUP98-NSD1 positive patients post-treatment.
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS foundation Trust, Birmingham, UK; School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Susanna
authors.initials: S
authors.lastname: Akiki
authors.forename: Sara A
authors.initials: SA
authors.lastname: Dyer
authors.forename: David
authors.initials: D
authors.lastname: Grimwade
authors.forename: Adam
authors.initials: A
authors.lastname: Ivey
authors.forename: Nervana
authors.initials: N
authors.lastname: Abou-Zeid
authors.forename: Julian
authors.initials: J
authors.lastname: Borrow
authors.forename: Sally
authors.initials: S
authors.lastname: Jeffries
authors.forename: Judith
authors.initials: J
authors.lastname: Caddick
authors.forename: Hayley
authors.initials: H
authors.lastname: Newell
authors.forename: Suriya
authors.initials: S
authors.lastname: Begum
authors.forename: Kiran
authors.initials: K
authors.lastname: Tawana
authors.forename: Joanne
authors.initials: J
authors.lastname: Mason
authors.forename: Mark
authors.initials: M
authors.lastname: Velangi
authors.forename: Michael
authors.initials: M
authors.lastname: Griffiths
mesh_terms: D000293:Adolescent; D001244:Association; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D050939:Gene Fusion; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D047908:Intracellular Signaling Peptides and Proteins; C000716967:NPM1 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C093350:nuclear pore complex protein 98; D000090243:Nucleophosmin; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3