NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern

Iris H.I.M. Hollink, Marry M. Van Den Heuvel-Eibrink, Susan T.C.J.M. Arentsen-Peters, Marta Pratcorona, Saman Abbas, Jenny E. Kuipers, Janneke F. Van Galen, H. Berna Beverloo, Edwin Sonneveld, Gert Jan J.L. Kaspers, Jan Trka, Andre Baruchel, Martin Zimmermann, Ursula Creutzig, Dirk Reinhardt, Rob Pieters, Peter J.M. Valk, C. Michel Zwaan

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

234 Citaten (Scopus)


Translocations involving nucleoporin 98kD (NUP98) on chromosome 11p15 occur at relatively low frequency in acute myeloid leukemia (AML) but can be missed with routine karyotyping. In this study, high-resolution genome-wide copy number analyses revealed cryptic NUP98/NSD1 translocations in 3 of 92 cytogenetically normal (CN) - AML cases. To determine their exact frequency, we screened > 1000 well-characterized pediatric and adult AML cases using a NUP98/NSD1-specific RT-PCR. Twenty-three cases harbored the NUP98/NSD1 fusion, representing 16.1% of pediatric and 2.3% of adult CN-AML patients. NUP98/NSD1-positive AML cases had significantly higher white blood cell counts (median, 147 × 109/L), more frequent FAB-M4/M5 morphology (in 63%), and more CN-AML (in 78%), FLT3/internal tandem duplication (in 91%) and WT1 mutations (in 45%) than NUP98/NSD1-negative cases. NUP98/NSD1 was mutually exclusive with all recurrent type-II aberrations. Importantly, NUP98/NSD1 was an independent predictor for poor prognosis; 4-year event-free survival was < 10% for both pediatric and adult NUP98/NSD1-positiveAML patients. NUP98/NSD1-positive AML showed a characteristic HOX-gene expression pattern, distinct from, for example, MLLrearranged AML, and the fusion protein was aberrantly localized in nuclear aggregates, providing insight into the leukemogenic pathways of these AMLs. Taken together, NUP98/NSD1 identifies a previously unrecognized group of young AML patients, with distinct characteristics and dismal prognosis, for whom new treatment strategies are urgently needed.

Originele taal-2Engels
Pagina's (van-tot)3645-3656
Aantal pagina's12
Nummer van het tijdschrift13
StatusGepubliceerd - 29 sep. 2011
Extern gepubliceerdJa


Duik in de onderzoeksthema's van 'NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern'. Samen vormen ze een unieke vingerafdruk.

Citeer dit