Expression of the novel NUP98/PSIP1 fusion transcripts in myelodysplastic syndrome with t(9;11)(p22;p15)

Eur J Haematol. 2012 Mar;88(3):244-8. doi: 10.1111/j.1600-0609.2011.01736.x. Epub 2012 Jan 16.

Abstract

Objectives: The t(9;11)(p22;p15) is a very rare but recurrent translocation in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) blast crisis. The translocation results in a fusion gene between NUP98 at 11p15 and PSIP1 encoding two transcriptional coactivators, p52 and p75, at 9p22. Here, we describe the first case of myelodysplastic syndrome (MDS) with t(9;11)(p22;p15).

Patient: A 64-yr-old woman presented pancytopenia, trilineage dysplasia, and 9.2% blasts in the bone marrow, indicating the diagnosis of MDS.

Results: G-banding and spectral karyotyping showed 46,XX,t(9;11)(p22;p15)[20]. Reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing detected four types of NUP98/PSIP1-p52 and two types of NUP98/PSIP1-p75 fusion transcripts. Essentially, the NUP98 exon 12 or exon 11 by alternative splicing was fused in-frame with the PSIP1 exon 8. Real-time quantitative (RQ) PCR for NUP98/PSIP1/GAPDH demonstrated a 4-log decrease after cord blood transplantation and a 2-log increase at relapse.

Conclusions: The fusion genes combining NUP98 exon 11/12 with PSIP1 exon 8, which have never been detected in other AML/CML cases, may be implicated in the pathogenesis of MDS. Furthermore, RQ-PCR for NUP98/PSIP1 could be useful to monitor minimal residual disease.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Base Sequence
  • Chromosome Banding
  • Chromosomes, Human, Pair 11*
  • Chromosomes, Human, Pair 9*
  • Exons
  • Female
  • Gene Order
  • Genes, Wilms Tumor
  • Humans
  • Middle Aged
  • Myelodysplastic Syndromes / genetics*
  • Nuclear Pore Complex Proteins / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Transcription Factors / genetics*
  • Translocation, Genetic*

Substances

  • Adaptor Proteins, Signal Transducing
  • NUP98-PSIP1 fusion protein, human
  • Nuclear Pore Complex Proteins
  • Nup98 protein, human
  • Oncogene Proteins, Fusion
  • PSIP1 protein, human
  • Transcription Factors