The t(1;12)(q21;p13) Translocation of Human Acute Myeloblastic Leukemia Results in a TEL-ARNT Fusion

• Published in: Proceedings of the National Academy of Sciences - PNAS 2000-06, Vol.97 (12), p.6757-6762
• Main Authors: Salomon-Nguyen, Florence, Della-Valle, Veronique, Mauchauffe, Martine, Coniat, Maryvonne Busson-Le, Ghysdael, Jacques, Berger, Roland, Bernard, Olivier A.
• Format: Article
• Language: English
• Subjects: Amino acids; Antiserum; Artificial Gene Fusion; Aryl Hydrocarbon Receptor Nuclear Translocator; Biological Sciences; Cell lines; Child, Preschool; chromosome 1; chromosome 12; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 12; DNA-Binding Proteins - genetics; ETS protein; ETS Translocation Variant 6 Protein; ETV gene; Genes; Humans; Hypoxia; hypoxia inducible factor 1a; Leukemia; Leukemia, Myeloid, Acute - genetics; Male; Medical research; nuclear translocators; Protein transport; Proteins; Proto-Oncogene Proteins c-ets; Receptors, Aryl Hydrocarbon; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; TEL gene; Transcription factors; Transcription Factors - genetics; Translocation, Genetic; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.120162297

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 1α (HIF1α ). 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 HIF1α can contribute to leukemogenesis.