Consistent Intergenic Splicing and Production of Multiple Transcripts Between AML1 at 21q22 and Unrelated Genes at 3q26 in (3;21)(q26;q22) Translocations

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 9; pp. 4004 - 4008
• Main Authors: Nucifora, Giuseppina, Begy, Catherine R., Kobayashi, Hirofumi, Roulston, Diane, Claxton, David, Pedersen-Bjergaard, Jens, Parganas, Evan, Ihle, James N., Rowley, Janet D.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 26-04-1994; National Acad Sciences; National Academy of Sciences
• Subjects: acute myeloid leukemia; Amino Acid Sequence; Amino acids; AML1 gene; Base Sequence; Biochemistry; Biological and medical sciences; chromosome 3; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 3; cloning; Complementary DNA; Core Binding Factor Alpha 2 Subunit; DNA Primers - chemistry; DNA-Binding Proteins - genetics; Employee assistance programs; Exons; fusion; Gels; Gene Expression Regulation, Neoplastic; Genes; Genetics; Hematologic and hematopoietic diseases; Humans; Leukemia; Leukemia - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; man; MDS1 and EVI1 Complex Locus Protein; Medical research; Medical sciences; Molecular Sequence Data; Myelodysplastic Syndromes - genetics; Myeloid leukemia; myeloproliferative diseases; Neoplasm Proteins - genetics; oncogenes; patients; prediction; Proto-Oncogene Proteins; Proto-Oncogenes; Recombinant Fusion Proteins - genetics; Reverse transcriptase polymerase chain reaction; Ribosomal Proteins; RNA Splicing; RNA, Messenger - genetics; RNA, Neoplasm - genetics; RNA-Binding Proteins - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Transcription Factors; translocation; Translocation, Genetic; Chromosomal aberration; Human; Iatrogenic; Acute; Malignant hemopathy; Genetic distance; Gene expression; Myelodysplastic syndrome; Gene rearrangement; Abnormal chromosome; A3-Chromosome; Hybrid gene; G21-Chromosome; Acute myelocytic leukemia; Chromosome translocation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.9.4004

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 therapyrelated 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.