Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt

• Published in: Blood Vol. 80; no. 7; pp. 1825 - 1831
• Main Authors: ERICKSON, P, GAO, J, CHANG, K.-S, LOOK, T, WHISENANT, E, RAIMONDI, S, LASHER, R, TRUJILLO, J, ROWLEY, J, DRABKIN, H
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 01.10.1992
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 8; Cloning, Molecular; DNA Probes; DNA-Binding Proteins - genetics; Drosophila - genetics; Genomic Library; Hematologic and hematopoietic diseases; Humans; Hybrid Cells; Leukemia, Myeloid, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Molecular Sequence Data; Nuclear Proteins - genetics; Protein Kinases - genetics; Rats; Restriction Mapping; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Transcription Factors - genetics; Transcription, Genetic; Translocation, Genetic; Chromosomal aberration; Human; Breakpoint; Abnormal chromosome; Exploration; Malignant hemopathy; Molecular biology; Acute myelocytic leukemia; Chromosome translocation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V80.7.1825.1825

We have developed a restriction map of the chromosome 21 breakpoint region involved in t(8;21)(q22;q22.3) acute myelogenous leukemia (AML) and have isolated a genomic junction clone containing chromosome 8 and 21 material. Using probes from these regions, rearrangements have been identified in each of nine cases of t(8;21) AML examined. In addition, we have isolated cDNA clones from a t(8;21) AML cDNA library that contain fused sequences from chromosome 8 and 21. The chromosome 8 component, referred to as ETO (for eight twenty-one), is encoded over a large genomic region, as suggested by the analysis of corresponding yeast artificial chromosomes (YACs). The DNA sequence of the chromosome 21 portion of the fusion transcript is derived from the normal AML1 gene. A striking similarity (67% identity over 387 bp, with a corresponding 69% amino acid identity) was detected between AML1 and the Drosophila segmentation gene, runt. The critical consequence of the translocation is the juxtaposition of 5' sequences of AML1 to 3' sequences of ETO, oriented telomere to centromere on the der(8) chromosome.