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

被引：57

作者：

Graux, C. ^{[1
,2
,3
,4
]}

Stevens-Kroef, M. ^{[5
]}

Lafage, M. ^{[6
]}

Dastugue, N. ^{[7
]}

Harrison, C. J. ^{[8
]}

Mugneret, F. ^{[9
]}

Bahloula, K. ^{[2
]}

Struski, S. ^{[10
]}

Gregoire, M. J. ^{[11
]}

Nadal, N. ^{[12
]}

Lippert, E. ^{[13
]}

Taviaux, S. ^{[14
]}

Simons, A. ^{[5
]}

Kuiper, R. P. ^{[5
]}

Moorman, A. V.

Barber, K. ^{[15
]}

Bosly, A. ^{[1
]}

Michaux, L. ^{[4
]}

Vandenberghe, P. ^{[4
]}

Lahortiga, I. ^{[3
,4
]}

De Keersmaecker, K. ^{[3
,4
]}

Wlodarska, I. ^{[4
]}

Cools, J. ^{[3
,4
]}

Hagemeijer, A. ^{[4
]}

Poirel, H. A. ^{[2
]}

机构：

[1] Clin Univ UCL Mont Godinne, Dept Hematol, B-5530 Yvoir, Belgium

[2] Clin Univ St Luc, Ctr Human Genet, Hematol Sect, B-1200 Brussels, Belgium

[3] VIB, Dept Mol & Dev Genet, Louvain, Belgium

[4] Univ Leuven, Ctr Human Genet, Louvain, Belgium

[5] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[6] CHU Timone, Dept Genet, Marseille, France

[7] Hop Purpan, Lab Hematol Genet Hemopathies, Toulouse, France

[8] Univ Newcastle, No Inst Canc Res, Leukamia Res Cytogenet Grp, Newcastle Upon Tyne, Tyne & Wear, England

[9] CHU Bocage, Lab Cytogenet, Dijon, France

[10] Hop Haute Pierre, Hematol Lab, Strasbourg, France

[11] CHU Nancy Brabois, Genet Lab, Vandoeuvre Les Nancy, France

[12] CHU Hop Nord, Lab Hematol Pavillon Biol, St Etienne, France

[13] CHU Bordeaux, Hematol Lab, Bordeaux, France

[14] Hop Arnaud Villeneuve, Lab Hematol Genet Mol & Chromosom, Montpellier, France

[15] Univ Southampton, Leukamia Res Cytogenet Grp, Canc Sci Div, Southampton, Hants, England

来源：

LEUKEMIA | 2009年 / 23卷 / 01期

关键词：

T-ALL; NUP214-ABL1; episomes; hsr; gene amplification; ABL1; PHENOTYPE; LINES;

D O I：

10.1038/leu.2008.278

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 nonamplified 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.

引用

页码：125 / 133

页数：9

共 27 条

[21]

Solovei I, 2000, GENE CHROMOSOME CANC, V29, P297, DOI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1046>3.0.CO

[22]

2-H

[23] Philadelphia chromosome-positive acute myeloid leukemia - A rare aggressive leukemia with clinicopathologic features distinct from chronic myeloid leukemia in myeloid blast crisis [J].

Soupir, Chad P. ;

Vergilio, Jo-Anne ;

Dal Cin, Paola ;

Muzikansky, Alona ;

Kantarjian, Hagop ;

Jones, Dan ;

Hasserjian, Robert P. .

AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2007, 127 (04) :642-650

[24]

Van Limbergen H, 2001, GENE CHROMOSOME CANC, V30, P274, DOI 10.1002/1098-2264(2000)9999:9999<1::AID-GCC1089>3.3.CO

[25]

2-T

[26]

WAHL GM, 1989, CANCER RES, V49, P1333

[27] The BCR-ABL story: Bench to bedside and back [J].

Wong, S ;

Witte, ON .

ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :247-306

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