User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

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

Primary tabs

download
  • Open access
  • PDF
  • 499.53 K
Graux, Carlos [UCL] Stevens-Kroef, M. Lafage, M. Dastugue, N. Harrison, C.J. Bahloula, Khadija [UCL] Bosly, André [UCL] Michaux, Lucienne [UCL] Vandenberghe, Pierre [UCL] Antoine-Poirel, Mathilde [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2009
Journal information "Leukemia" - Vol. 23, no. 1, p. 125-133 (2009)
Peer reviewed yes
Publisher Nature Publishing Group ((United Kingdom) London)
issn 0887-6924
e-issn 1476-5551
Publication status Publié
Affiliations UCL - (MGD) Service d'hématologie
UCL - MD/MINT - Département de médecine interne
MESH Subject Adolescent ; Adult ; Cell Line, Tumor ; Child ; Child, Preschool ; Female ; Gene Amplification ; Homeodomain Proteins - genetics ; Humans ; Leukemia-Lymphoma, Adult T-Cell - etiology - genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion - genetics ; Plasmids ; Proto-Oncogene Proteins - genetics ; Sex Factors ; Treatment Outcome ; Young Adult
Keywords T-ALL ; NUP214-ABL1 ; Episomes ; hsr ; Gene amplification
Links
  1. Wong S, Annu Rev Immunol, 22, 247 (2004)
  2. Pui CH, N Engl J Med, 350, 1535 (2004)
  3. Soupir CP, Am J Clin Pathol, 127, 642 (2007)
  4. Melo JV, Blood, 88, 2375 (1996)
  5. Van Limbergen H, Genes Chromosomes Cancer, 30, 274 (2001)
  6. De Braekeleer E, Leukemia, 21, 2220 (2007)
  7. Quentmeier H, Leukemia, 19, 295 (2005)
  8. Barber KE, Leukemia, 18, 1153 (2004)
  9. Graux C, Nat Genet, 36, 1084 (2004)
  10. Ballerini P, Leukemia, 19, 468 (2005)
  11. De Keersmaecker K, Blood, 105, 4849 (2005)
  12. De Keersmaecker K, Leukemia, 20, 2202 (2006)
  13. Graux C, Leukemia, 20, 1496 (2006)
  14. Quintás-Cardama A, Leukemia, 22, 1117 (2008)
  15. Bene MC, Leukemia, 9, 1783 (1995)
  16. Ravid Z, Int J Cancer, 25, 705 (1980)
  17. De Keersmaecker K, Mol Cell, 31, 134 (2008)
  18. Hurley EA, J Virol, 65, 1245 (1991)
  19. Shimizu N, Experimental Cell Research, 302, 233 (2005)
  20. Solovei I, Genes Chromosomes Cancer, 29, 297 (2000)
  21. Wahl GM, Cancer Res, 49, 1333 (1989)
  22. Levis M, Blood, 104, 1145 (2004)
Bibliographic reference Graux, Carlos ; Stevens-Kroef, M. ; Lafage, M. ; Dastugue, N. ; Harrison, C.J. ; et. al. Heterogeneous patterns of amplification of the NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia. In: Leukemia, Vol. 23, no. 1, p. 125-133 (2009)
Permanent URL http://hdl.handle.net/2078.1/29423