title: Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.
abstract: Chromosomal rearrangements involving band 12p13 are found in a wide variety of human leukemias but are particularly common in childhood acute lymphoblastic leukemia. The genes involved in these rearrangements, however, have not been identified. We now report the cloning of a t(12;21) translocation breakpoint involving 12p13 and 21q22 in two cases of childhood pre-B acute lymphoblastic leukemia, in which t(12;21) rearrangements were not initially apparent. The consequence of the translocation is fusion of the helix-loop-helix domain of TEL, an ETS-like putative transcription factor, to the DNA-binding and transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor. The TEL-AML1 fusion also indicates that translocations affecting the AML1 gene can be associated with lymphoid, as well as myeloid, malignancy.
authors.affiliation: Division of Hematology/Oncology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Golub
authors.forename: G F
authors.initials: GF
authors.lastname: Barker
authors.forename: S K
authors.initials: SK
authors.lastname: Bohlander
authors.forename: S W
authors.initials: SW
authors.lastname: Hiebert
authors.forename: D C
authors.initials: DC
authors.lastname: Ward
authors.forename: P
authors.initials: P
authors.lastname: Bray-Ward
authors.forename: E
authors.initials: E
authors.lastname: Morgan
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: J D
authors.initials: JD
authors.lastname: Rowley
authors.forename: D G
authors.initials: DG
authors.lastname: Gilliland
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D002675:Child, Preschool; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D015321:Gene Rearrangement; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007621:Karyotyping; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human; C102421:TEL-AML1 fusion protein