The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern
Abstract
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-positive AML patients. NUP98/NSD1-positive AML showed a characteristic HOX-gene expression pattern, distinct from, for example, MLL-rearranged 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.
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Cites
Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype
Falini, B., Mecucci, C., Tiacci, E., Alcalay, M., Rosati, R., Pasqualucci, L., La Starza, R., Diverio, D., Colombo, E., Santucci, A., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa041974 · Cited by 1,892
Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia
Valk, P. J. M., Verhaak, R. G. W., Beijen, M. A., Erpelinck, C. A. J., van Doorn-Khosrovani, S. B. V. W., Boer, J. M., Beverloo, H. B., Moorhouse, M. J., van der Spek, P. J., Löwenberg, B., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040465 · Cited by 1,370
Self-citationHox genes in hematopoiesis and leukemogenesis
Argiropoulos, B., & Humphries, R. K. (2007) · Oncogene · doi:10.1038/sj.onc.1210760 · Cited by 492
Cited by
Bolouri, H., Farrar, J. E., Triche, T., Ries, R. E., Lim, E. L., Alonzo, T. A., Ma, Y., Moore, R., Mungall, A. J., Marra, M. A., et al. (2018) · Nature Medicine · doi:10.1038/nm.4439 · Cited by 848
Self-citation(2013) · doi:10.1158/2159-8290.cd-13-0350 · Cited by 393
Critical roles of non-histone protein lysine methylation in human tumorigenesis
Hamamoto, R., Saloura, V., & Nakamura, Y. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3884 · Cited by 376
Metadata
- Authors
- Hollink, I. H. I. M., van den Heuvel-Eibrink, M. M., Arentsen-Peters, S. T. C. J. M., Pratcorona, M., Abbas, S., Kuipers, J. E., van Galen, J. F., Beverloo, H. B., Sonneveld, E., Kaspers, G.-J. J. L., Trka, J., Baruchel, A., Zimmermann, M., Creutzig, U., Reinhardt, D., Pieters, R., Valk, P. J. M., & Zwaan, C. M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-09-29
- Volume
- 118
- Issue
- 13
- Pages
- 3645-3656
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1974119365
- Cited by
- 334
- References
- 3
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Hollink, I. H. I. M., van den Heuvel-Eibrink, M. M., Arentsen-Peters, S. T. C. J. M., Pratcorona, M., Abbas, S., Kuipers, J. E., van Galen, J. F., Beverloo, H. B., Sonneveld, E., Kaspers, G.-J. J. L., Trka, J., Baruchel, A., Zimmermann, M., Creutzig, U., Reinhardt, D., Pieters, R., Valk, P. J. M., & Zwaan, C. M. (2011). NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood. https://doi.org/10.1182/blood-2011-04-346643
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
