The cardiac homeobox gene NKX2-5 is deregulated by juxtaposition with BCL11B in pediatric T-ALL cell lines via a novel t(5;14)(q35.1;q32.2).
The cardiac homeobox gene NKX2-5 is deregulated by juxtaposition with BCL11B in pediatric T-ALL cell lines via a novel t(5;14)(q35.1;q32.2).
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发表时间：
2003-09
期刊：
影响因子：
11.2
通讯作者：
S. Nagel;M. Kaufmann;H. Drexler;R. MacLeod
中科院分区：
文献类型：
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作者：
S. Nagel;M. Kaufmann;H. Drexler;R. MacLeod
最近在儿童急性淋巴细胞白血病（ALL）中发现了一种隐藏的染色体重排，t（5;14）（q35.1;q32.2），靶向5q35.1的TLX 3激活，与14q32.2的BCL 11 B下游区域并置。我们描述了一种新的变体t（5;14），其中NKX 2 -5，一个相关的（NK样家族）同源异型盒基因位于TLX 3端粒的约2 Mb处，并置在T细胞ALL细胞系的一个子集中的BCL 11 B。在该t（5;14）变体中，NKX 2 -5在RNA和蛋白质水平上表达而不是TLX 3。随后的表达筛选未能检测到T细胞ALL细胞中其他NK样基因的参与。我们的数据指出了BCL 11B影响异位同源异型盒基因激活的下游调控区。本研究还确定了两种t（5;14）变异体的体外模型，并提出了关于ALL诊断荧光原位杂交/逆转录PCR筛查的问题。
A cryptic chromosome rearrangement, t(5;14)(q35.1;q32.2), recently identified in pediatric acute lymphoblastic leukemia (ALL), targets activation of TLX3 at 5q35.1 by juxtaposition with a region downstream of BCL11B at 14q32.2. We describe a novel variant t(5;14) whereby NKX2-5, a related (NK-like family) homeobox gene located approximately 2 Mb telomeric of TLX3, juxtaposes BCL11B in a subset of T-cell ALL cell lines. In this t(5;14) variant, NKX2-5 is expressed instead of TLX3 at both RNA and protein levels. Subsequent expression screening failed to detect involvement of additional NK-like genes in T-cell ALL cells. Our data pinpoint a regulatory region far downstream of BCL11B effecting ectopic homeobox gene activation. This study also identifies in vitro models for both t(5;14) variants and raises questions about diagnostic fluorescence in situ hybridization/reverse transcription-PCR screening in ALL.