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Cancer Res. 2003 Sep 1;63(17):5329-34.

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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  • 1DSMZ, Department of Human and Animal Cell Cultures, 38124 Braunschweig, Germany.

Abstract

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.

PMID:
14500364
[PubMed - indexed for MEDLINE]
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