The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion

摘要

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 un- related transcription factors or protein tyrosine kinasei. We have characterized a t(1;12)(q21;p13) translocation in an acute myelo- blastic 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 recep- tor nuclear translocator (ARNT) are expressed. The involvement of ARNT in human leukemogenesis has not been previously de- scribed. 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 1_α (HIF1_α). 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 HIF1_α can contribute to leukemogenesis.