Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation

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.Our results show that fusion of the NUP98 and LEDGF genes is a new recurrent translocation in AML.The translocation, t(9;11)(p22;p15), was first reported in a patient with AML M1 [1]. Recently, a second AML M1 patient with a cytogenetically identical translocation was shown to have a fusion transcript between the 5' end of the NUP98 gene on 11p15 and the 3' end of the LEDGF gene on 9p22 [2].We have identified a third AML patient with a cytogenetically identical translocation. The patient, a 60 year old Caucasian woman presented with a white cell count of 1.5 x 109/L due to neutropenia. The bone marrow showed 50% blasts and 30% promyelocytes. She was diagnosed as AML M2. Cytogenetics showed 46,XX,t(9;11)(p22;p15) [13 cells]/46,XX [2 cells]. Induction chemotherapy with ARA-C, idarubicin and etoposide was abandoned after the patient developed a severe neutropenic reaction at the end of the first course. Nevertheless, complete haematological and cytogenetic remission was obtained. After 54 months, the patient relapsed with frank leukemia and a white cell count of 50 x 109/L. Due to the patient's wishes, only supportive therapy was given, and she died of her disease a few days later with a rapidly escalating blast cell burden. Cytogenetics of the relapse perip