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).
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.
D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000235:genetics*
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D029867:Xenopus Proteins