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Heterogeneous patterns of amplification of the NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia

Lookup NU author(s): Professor Christine Harrison FRCPath FMedSci, Professor Anthony Moorman

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Abstract

Episomes with the NUP214-ABL1 fusion gene have been observed in 6% of T-ALL. In this multicentric study we collected 27 cases of NUP214-ABL1-positive T-ALL. Median age was 15 years with male predominance. Outcome was poor in 12 patients. An associated abnormality involving TLX1 or TLX3 was found in all investigated cases. Fluorescent in situ hybridization revealed a heterogeneous pattern of NUP214-ABL1 amplification. Multiple episomes carrying the fusion were detected in 24 patients. Episomes were observed in a significant number of nuclei in 18 cases, but in only 1-5% of nuclei in 6. In addition, intrachromosomal amplification (small hsr) was identified either as the only change or in association with episomes in four cases and two T-ALL cell lines (PEER and ALL-SIL). One case showed insertion of apparently non-amplified NUP214-ABL1 sequences at 14q12. The amplified sequences were analyzed using array-based CGH.These findings confirm that the NUP214-ABL1 gene requires amplification for oncogenicity; it is part of a multistep process of leukemogenesis; and it can be a late event present only in subpopulations. Data also provide in vivo evidence for a model of episome formation, amplification and optional reintegration into the genome. Implications for the use of kinase inhibitors are discussed.Leukemia advance online publication, 16 October 2008; doi:10.1038/leu.2008.278.


Publication metadata

Author(s): Graux C, Stevens-Kroef M, Lafage M, Dastugue N, Harrison CJ, Mugneret F, Bahloula K, Struski S, Grégoire MJ, Nadal N, Lippert E, Taviaux S, Simons A, Kuiper RP, Moorman AV, Barber K, Bosly A, Michaux L, Vandenberghe P, Lahortiga I, De Keersmaecker K, Wlodarska I, Cools J, Hagemeijer A, Poirel HA

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2009

Volume: 23

Issue: 1

Pages: 125-133

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/leu.2008.278

DOI: 10.1038/leu.2008.278

Notes: Journal article official journal of the Leukemia Society of America, Leukemia Research Fund, U.K


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