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DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen), Department of Human and Animal Cell Cultures, 38124 Braunschweig, Germany [S. N., M. K., H. G. D., R. A. F. M.]
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 
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.
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