Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations.
Two genes have been implicated in leukemias of patients with abnormalities of chromosome 3, band q26: EVI1, which can be activated over long distances by chromosomal rearrangements involving 3q26, and EAP, a ribosomal gene that fuses with AML1 in a therapy-related myelodysplasia patient with a t(3;21)(q26.2;q22). AML1 was identified by its involvement in the t(8;21)(q22;q22) of acute myeloid leukemia. Here we report the consistent identification of fusion transcripts between AML1 and EAP or between AML1 and previously unidentified sequences that we named MDS1 (MDS-associated sequences) in the leukemic cells of four patients with therapy-related myelodysplasia/acute myeloid leukemia and in one patient with chronic myelogenous leukemia in blast crisis, all of whom had a t(3;21). In addition, we have identified a third chimeric transcript, AML1/EVI1, in one of the therapy-related acute myeloid leukemia patients. Pulsed-field gel electrophoresis established the order of the genes as EAP, the most telomeric, and EVI1, the most centromeric, gene. The results indicate that translocations could involve multiple genes and affect gene expression over long distances.
Nucifora
G
G
Department of Medicine, University of Chicago, IL 60637.
Begy
C R
CR
Kobayashi
H
H
Roulston
D
D
Claxton
D
D
Pedersen-Bjergaard
J
J
Parganas
E
E
Ihle
J N
JN
Rowley
J D
JD
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D002893:Chromosomes, Human, Pair 3; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012269:Ribosomal Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C493728:RUNX1 protein, human; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; D014157:Transcription Factors; C067169:RPL22 protein, human