The effect of a novel recombination between the homeobox gene NKX2-5 and the TRD locus in T-cell acute lymphoblastic leukemia on activation of the NKK2-5 gene

Grzeogrz K. Przybylski, Wim Dik, Piotr Grabarczyk, Jens Wanzeck, Paulina Chudobska, Kacper Jankowski, Anne von Bergh, Jacques J.M. van Dongen, Christine A. Schmidt, Anton W. Langerak

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background and Objectives. The NK-like homeobox gene (NKX2-5/CSX) plays a crucial
role in cardiac development but is not normally expressed in hematopoietic cells. Here,
we describe for the first time a fusion between NKX2-5 and the T-cell receptor delta
locus (TRD) resulting in NKX2-5 activation in a case of T-cell acute lymphoblastic
leukemia (T-ALL).
Design and Methods. Genomic DNA from a T-ALL patient with an atypical rearrangement,
detected by Southern blotting, was analyzed by ligation-mediated polymerase
chain reaction (PCR) with TRD-specific primers. Expression of NKX2-5 was analyzed by
real-time quantitative PCR in the T-ALL case with the NKX2-5-TRD rearrangement, 18
other cases of T-ALL, three T-ALL derived cell lines, two non-hematopoietic cell lines,
peripheral blood mononuclear cells from six healthy individuals and sorted thymocyte
subsets.
Results. Sequence analysis of ligation-mediated PCR products revealed a novel
rearrangement between the third diversity segment of the TRD locus (TRDD3) and a
region on chromosome 5q35.1 located 32 kb downstream of the NKX2-5/CSX gene.
As a result of this recombination NKX2-5 was placed under influence of the TRD
enhancer, resulting in strong ectopic NKX2-5 expression. High NKX2-5 expression was
also found in the T-cell lines PEER and CCRF-CEM, which harbor an NKX2-5-BCL11B
rearrangement, and in the embryonic kidney cell line 293. NKX2-5 was not expressed
in any of the major thymocyte subsets, in normal peripheral blood mononuclear cells,
or in the majority (17/18) of the other cases of T-ALL.
Interpretation and Conclusions. Our finding of overexpression of yet another homeobox
gene in T-ALL further supports the hypothesis that homeobox genes play an important
role in malignant transformation of particular types of T-ALL.
Original languageEnglish
Pages (from-to)317-321
Number of pages5
JournalHaematologica
Volume91
Issue number3
Publication statusPublished - Mar 2006

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  • EMC MM-02-72-03

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