Transcriptional activation of the cardiac homeobox gene CSX1/NKX2-5 in a B-cell chronic lymphoproliferative disorder

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Haematologica 2008, 10.3324/haematol.12595

Transcriptional activation of the cardiac homeobox gene CSX1/NKX2-5 in a B-cell

chronic lymphoproliferative disorder

Xinying Su1,5, Véronique Della-Valle1,5, Delabesse3, Zahia Azgui2, Roland

Berger1, Hélène Merle-Béral2,4, Olivier A Bernard1,5, Florence Nguyen-Khac1,2,4

1 INSERM, E0210, Hôpital Necker, Paris

2 Service d'Hematologie Biologique, Groupe Hospitalier Pitie-Salpetriere, Paris

3 Laboratoire d'Hématologie, CHU Purpan, Toulouse

4 Université Pierre et Marie Curie, Paris VI

5 Université Rene Descartes, Paris V, France

Correspondence: Florence Nguyen-Khac, Service d'Hematologie Biologique Groupe

Hospitalier Pitié-Salpetriére, Pavillon Laveran, 47-83 Bd de l'Hopital, 75013

Paris, France. E-mail:florence.nguyen@...

ABSTRACT

Homeobox containing transcription factors are frequently deregulated in human

hematologic malignant diseases either indirectly through an abnormality of an

upstream factor, or directly through rearrangement of the gene itself. Study of

T-cell acute lymphoblastic leukemia identified the related non-clustered

homeobox transcription factors, TLX1 and TLX3, as frequently ectopically

expressed as a result of chromosomal translocations. We report the deregulation

of a non-clustered homeobox gene in a new type of t(5;14)(q35;q11) translocation

in a mature peripheral B-cell leukemia. This translocation results in the

ectopic expression of the CSX1/NKX2-5 gene on chromosome 5q35 due to its

juxtaposition to the TCR gene on chromosome 14q11. Expression of the

CSX1/NKX2-5 protein conferred enhanced replating potential to transduced murine

bone marrow cells. Our study establishes that deregulation of homeobox encoding

genes is not restricted to acute leukemic proliferations, but is also observed

in chronic malignant diseases.