The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1.
In the 8;21 translocation, the AML1 gene, located at chromosome band 21q22, is translocated to chromosome 8 (q22), where it is fused to the ETO gene and transcribed as a chimeric gene. AML1 is the human homolog of the recently cloned mouse gene pebp2 alpha B, homologous to the DNA binding alpha subunit of the polyoma enhancer factor pebp2. AML1 is also involved in a translocation with chromosome 3 that is seen in patients with therapy-related acute myeloid leukemia and myelodysplastic syndrome and in chronic myelogenous leukemia in blast crisis. We have isolated a fusion cDNA clone from a t(3;21) library derived from a patient with therapy-related myelodysplastic syndrome; this clone contains sequences from AML1 and from EAP, which we have now localized to band 3q26. EAP has previously been characterized as a highly expressed small nuclear protein of 128 residues (EBER 1) associated with Epstein-Barr virus small RNA. The fusion clone contains the DNA binding 5' part of AML1 that is fused to ETO in the t(8;21) and, in addition, at least one other exon. The translocation replaces the last nine codons of AML1 with the last 96 codons of EAP. The fusion does not maintain the correct reading frame of EAP and may not lead to a functional chimeric protein.
Department of Medicine, University of Chicago, IL 60637.
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G
Nucifora
C R
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Begy
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P
Erickson
H A
HA
Drabkin
J D
JD
Rowley
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D016466:CHO Cells; D002478:Cells, Cultured; D002678:Chimera; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D002893:Chromosomes, Human, Pair 3; D050676:Core Binding Factor Alpha 2 Subunit; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012367:RNA, Viral / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012269:Ribosomal Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C493728:RUNX1 protein, human; D012269:Ribosomal Proteins; D014157:Transcription Factors; C067169:RPL22 protein, human