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.

Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus / M. Alcalay, D. Zangrilli, P.P. Pandolfi, L. Longo, A. Mencarelli, A. Giacomucci, M. Rocchi, A. Biondi, A. Rambaldi, F. Lo Coco, D. Diverio, E. Donti, F. Grignani, P.G. Pelicci. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 88:5(1991), pp. 1977-1981. [10.1073/pnas.88.5.1977]

Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus

M. Alcalay;A. Rambaldi;P.G. Pelicci
1991

Abstract

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.
leukemogenesis; rearrangements
Settore MED/03 - Genetica Medica
Settore MED/15 - Malattie del Sangue
Article (author)
File in questo prodotto:
File Dimensione Formato  
O6-PNAS_Alcalay_91.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.4 MB
Formato Adobe PDF
1.4 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/810442
Citazioni
  • ???jsp.display-item.citation.pmc??? 43
  • Scopus 235
  • ???jsp.display-item.citation.isi??? 269
social impact