title: Transcriptional activation of the cardiac homeobox gene CSX1/NKX2-5 in a B-cell chronic lymphoproliferative disorder.
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 delta 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.
authors.affiliation: 1INSERM, E0210, Hôpital Necker, Paris, France.
authors.forename: Xinying
authors.initials: X
authors.lastname: Su
authors.forename: Véronique
authors.initials: V
authors.lastname: Della-Valle
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Zahia
authors.initials: Z
authors.lastname: Azgui
authors.forename: Roland
authors.initials: R
authors.lastname: Berger
authors.forename: Hélène
authors.initials: H
authors.lastname: Merle-Béral
authors.forename: Olivier A
authors.initials: OA
authors.lastname: Bernard
authors.forename: Florence
authors.initials: F
authors.lastname: Nguyen-Khac
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D002908:Chronic Disease; D003582:Cytogenetics; D005260:Female; D005786:Gene Expression Regulation; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014178:Translocation, Genetic
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors