The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.
The TEL/ETV6 gene is located at 12p13 and encodes a member of the ETS family of transcription factors. Translocated ETS leukemia (TEL) is frequently involved in chromosomal translocations in human malignancies, usually resulting in the expression of fusion proteins between the amino-terminal part of TEL and either unrelated transcription factors or protein tyrosine kinases. We have characterized a t(1;12)(q21;p13) translocation in an acute myeloblastic leukemia (AML-M2). At the protein level, the untranslocated TEL copy and, as a result of the t(1;12) translocation, a fusion protein between TEL and essentially all of aryl hydrocarbon receptor nuclear translocator (ARNT) are expressed. The involvement of ARNT in human leukemogenesis has not been previously described. The ARNT protein belongs to a subfamily of the "basic region helix-loop-helix" (bHLH) protein that shares an additional region of similarity called the PAS (Per, ARNT, SIM) domain. ARNT is the central partner of several heterodimeric transcription factors, including those containing the aryl hydrocarbon (dioxin) receptor (AhR) and the hypoxia-inducible factor 1alpha (HIF1alpha). Our results show that the TEL-ARNT fusion protein is the crucial product of the translocation and suggest that interference with the activity of AhR or HIF1alpha can contribute to leukemogenesis.
Salomon-Nguyen
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F
U434 Institut National de la Santé et de la Recherche Médicale-Centre d'Etude du Polymorphisme Humain-Fondation Jean Dausset, 27 rue Juliette Dodu, 75010, Paris, France.
Della-Valle
V
V
Mauchauffe
M
M
Busson-Le Coniat
M
M
Ghysdael
J
J
Berger
R
R
Bernard
O A
OA
D019677:Artificial Gene Fusion; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D050783:Proto-Oncogene Proteins c-ets; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C497396:ARNT protein, human