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

Genes Chromosomes Cancer. 2013 Nov;52(11):1053-64. doi: 10.1002/gcc.22100. Epub 2013 Sep 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Association
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Child
  • Child, Preschool
  • Gene Fusion*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy
  • Mutation*
  • Nuclear Pore Complex Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Intracellular Signaling Peptides and Proteins
  • NPM1 protein, human
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • nuclear pore complex protein 98
  • Nucleophosmin
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • NSD1 protein, human
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3