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Blood, 1 July 2005, Vol. 106, No. 1, pp. 274-286.
Prepublished online as a Blood First Edition Paper on March 17, 2005; DOI 10.1182/blood-2004-10-3900.
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Submitted October 7, 2004
Accepted February 27, 2005
HOXA genes are included in genetic and biological networks defining human acute T-cell leukemia (T-ALL)
Jean Soulier, Emmanuelle Clappier, Jean-Michel Cayuela, Armelle Regnault, Marina Garcia-Pedro, Herve Dombret, Andre Baruchel, Maria-Luisa Toribio, and Francois Sigaux*
INSERM U462 'Lymphocyte et Cancer', Institut Universitaire d'Hematologie, Hopital Saint Louis, Paris, France; Molecular Hematology Laboratory, Institut Universitaire d'Hematologie, Hopital Saint Louis, Paris, France
INSERM U462 'Lymphocyte et Cancer', Institut Universitaire d'Hematologie, Hopital Saint Louis, Paris, France
Centro de Biologia Molecular Severo Ochoa, CSIC, Universidad Autonoma de Madrid, Madrid, Spain
INSERM U462 'Lymphocyte et Cancer', Institut Universitaire d'Hematologie, Hopital Saint Louis, Paris, France; Adult Hematology Department, Hopital Saint-Louis, Paris, France
INSERM U462 'Lymphocyte et Cancer', Institut Universitaire d'Hematologie, Hopital Saint Louis, Paris, France; Pediatric Hematology Department, Hopital Saint Louis, Paris, France
* Corresponding author; email: fs{at}chu-stlouis.fr.
Using a combination of molecular cytogenetic and large-scale expression analysis in human T-ALL, we identified and characterized a new recurrent chromosomal translocation, targeting the major homeobox gene cluster HOXA and the TCRB locus. Specific quantitative PCR analysis showed that the expression of the whole HOXA gene cluster was dramatically dysregulated in the HOXA-rearranged cases, and also in MLL and CALM-AF10-related T-ALL cases, strongly suggesting that HOXA genes are oncogenic in these leukemias. Inclusion of HOXA-translocated cases in a general molecular portrait of 92 T-ALL based on large-scale expression analysis shows that this rearrangement defines a new homogeneous subgroup, which shares common biological networks with the TLX1 and TLX3-related cases. Since T-ALLs derive from T-cell progenitors, expression profiles of the distinct T-ALL subgroups were analyzed with respect to those of normal human thymic sub-populations. Inappropriate utilization or perturbation of specific molecular networks involved in thymic differentiation was detected. Moreover, we found a significant association between T-ALL oncogenic subgroups and ectopic expression of a limited set of genes, including several developmental genes, namely HOXA, TLX1, TLX3, NKX3-1, SIX6 and TFAP2C. These data strongly support the view that the abnormal expression of developmental genes, including the prototypical homeobox genes HOXA, is critical in T-ALL oncogenesis.
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[Full Text]
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|
|
|
|
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|
|
|
|
|
|
|
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October 1, 2007;
110(7):
2324 - 2330.
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[Full Text]
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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109(9):
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[Full Text]
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|
|
|
|
|
|
|
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|
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|
|
|
|
|
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|
|
|
|
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|
|
|
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|
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