NUP98-MLL fusion in human acute myeloblastic leukemia

被引：24

作者：

Kaltenbach, Sophie ^{[1
]}

Soler, Gwendoline ^{[2
,3
]}

Barin, Carole ^{[4
]}

Gervais, Carine ^{[5
]}

Bernard, Olivier A. ^{[1
,6
]}

Penard-Lacronique, Virginie ^{[1
,6
]}

Romana, Serge P. ^{[2
,3
]}

机构：

[1] Inst Gustave Roussy, INSERM, U985, F-94805 Villejuif, France

[2] Hop Necker Enfants Malad, AP HP, Lab Cytogenet, Paris, France

[3] Fac Paris Descartes, Paris, France

[4] CHU Tours, Lab Cytogenet, Tours, France

[5] CHU Strasbourg, Dept Hematol & Oncol, Strasbourg, France

[6] Fac Paris XI, Orsay, France

来源：

BLOOD | 2010年 / 116卷 / 13期

关键词：

HEMATOPOIETIC MALIGNANCIES; NUCLEAR-PORE; EXPRESSION; PROTEIN; GENES; MLL; DYSREGULATION; COFACTOR; MENIN;

D O I：

10.1182/blood-2010-04-277806

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Posttranscriptional modifications of histones play important roles in the control of chromatin structure and transcription. H3K4 (histone H3 lysine 4) methylation by the SET domain of the trithorax-group protein MLL (mixed-lineage leukemia) is important for the control of homeobox (HOX) gene expression during development. MLL is tethered to the HOXA locus through interaction of its amino-terminus with menin. MLL fusion proteins associated with human leukemia contain the menin interaction peptide and frequently recruit H3K79 (histone H3 lysine 79) methylation activity. This allows sustained expression of HOXA genes important for cellular transformation. We have characterized a novel recurrent chromosomal aberration, inv(11)(p15q23), as an isolated chromosomal abnormality in 2 patients with acute myeloid leukemia. This aberration is predicted to result in the expression of an NUP98 (nucleoporin 98 kDa)-MLL fusion protein that is unable to interact with menin. As expected, low levels of HOXA gene expression were observed in the patients' samples. This fusion protein is predicted to participate in cellular transformation by activating MLL targets other than HOXA genes. (Blood. 2010;116(13):2332-2335)

引用

页码：2332 / 2335

页数：4

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