Translocation Breakpoint of Acute Promyelocytic Leukemia Lies Within the Retinoic Acid Receptor α Locus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 5; pp. 1977 - 1981
• Main Authors: Alcalay, Myriam, Zangrilli, Daniela, Pandolfi, Pier Paolo, Longo, Letizia, Mencarelli, Amedea, Giacomucci, angelo, Rocchi, Mariano, Biondi, Andrea, Rambaldi, Alessandro, Lo Coco, Francesco, Diverio, Daniela, Donti, Emilio, Grignani, Fausto, Pelicci, Pier Giuseppe
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.03.1991; National Acad Sciences
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blotting, Southern; Carrier Proteins - genetics; Cell Line; Chromosomes; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Cloning, Molecular; Complementary DNA; DNA; DNA probes; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Enzymes; Exons; Genes; Genetic loci; Genomic Library; Genomics; Hematologic and hematopoietic diseases; Humans; Hybrid Cells - cytology; Leukemia, Promyelocytic, Acute - genetics; Leukemia, Promyelocytic, Acute - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lung; Medical sciences; Molecular Sequence Data; Nucleotides; Receptors, Retinoic Acid; Restriction Mapping; Sequence Homology, Nucleic Acid; Translocation, Genetic; Tretinoin - metabolism; Chromosomal aberration; Genetic mapping; Human; Breakpoint; Nucleotide sequence; Malignant hemopathy; Carcinogenesis; E17-Chromosome; D15»-Chromosome; Abnormal chromosome; Chromosome DNA; Retinoic acid; Acute myelocytic leukemia; Biological receptor; Chromosome translocation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.5.1977

Acute promyelocytic leukemias (APLs) are characterized by a reciprocal balanced translocation that involves chromosomes 15 and 17 [t(15;17)]. We report the isolation and characterization of one of the two reciprocal break sites and demonstrate that the chromosome 17 breakpoint lies within the retinoic acid receptor α locus. Nucleotide sequencing of the 15;17 cross-over junction on 15q+ showed that the retinoic acid receptor α gene is truncated within its first intron, 370 base pairs upstream from the splicing donor site of exon II. Such a recombination would be expected to generate abnormal RARα mRNA and protein. Southern blot analysis of a number of APLs with chromosome 15- and 17-derived DNA probes revealed similar 15;17 recombinations in the majority of other APLs. Our data are strong evidence that the retinoic acid receptor α gene plays a crucial role in the leukemogenesis of APL.