NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia

Cancer Res. 1998 Oct 1;58(19):4269-73.

Abstract

A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocation. We used rapid amplification of cDNA ends to identify a chimeric mRNA. An in-frame, chimeric mRNA that fused NUP98 sequences to the homeobox gene HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is structurally similar to the NUP98-HOXA9 fusion previously identified in patients with AML, leading to the speculation that NUP98-homeobox gene fusions may be oncogenic. Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may be a previously unsuspected target for chromosomal translocations in patients with t-AML.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Artificial Gene Fusion
  • Bone Marrow Cells / pathology
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11*
  • Chromosomes, Human, Pair 2*
  • Gene Rearrangement*
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Leukemia, Myeloid, Acute / chemically induced*
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • Neoplasms, Second Primary / chemically induced
  • Neoplasms, Second Primary / genetics
  • Nuclear Pore Complex Proteins*
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Recombinant Fusion Proteins / biosynthesis
  • Transcription Factors*
  • Translocation, Genetic*

Substances

  • HOXD13 protein, human
  • Homeodomain Proteins
  • Membrane Proteins
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Transcription Factors
  • nuclear pore complex protein 98