Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation.
BACKGROUND
The NUP98 gene is involved in multiple rearrangements in haematological malignancy. The leukemic cells in an acute myeloid leukemia (AML) patient with a t(9;11)(p22;p15) were recently shown to have a fusion between the NUP98 gene and the LEDGF gene but it was not demonstrated that this fusion was recurrent in other leukaemia patients with the same translocation.


RESULTS
We used RT-PCR to analyse the leukemic cells from an AML patient who presented with a cytogenetically identical translocation as the sole chromosomal abnormality. A NUP98-LEDGF fusion transcript was observed and confirmed by sequencing. The reciprocal transcript was also observed. The fusion transcript was not detectable during remission and recurred at relapse. The breakpoints in the NUP98 and LEDGF genes were different to those previously reported. The NUP98 breakpoint occurs in the intron between exons 8 and 9. It is the most 5' breakpoint reported in a translocation involving the NUP98 gene. All of the LEDGF gene is included in the fusion except for exon 1 which codes for the first 24 amino terminal amino acids.


CONCLUSIONS
Our results show that fusion of the NUP98 and LEDGF genes is a new recurrent translocation in AML.
Hussey
D J
DJ
Department of Haematology-Oncology, The Queen Elizabeth Hospital Woodville, SA 5011, Australia. damian.hussey@adelaide.edu.au
Moore
S
S
Nicola
M
M
Dobrovic
A
A
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012008:Recurrence; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D036341:Intercellular Signaling Peptides and Proteins; C469926:NUP98-LEDGF fusion protein, human; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D015514:Oncogene Proteins, Fusion; C504649:PSIP1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C119380:lens epithelium-derived growth factor