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

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

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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.

Original language	English
Pages (from-to)	1977-1981
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	88
Issue number	5
Publication status	Published - 1991

Keywords

leukemogenesis
rearrangements

ASJC Scopus subject areas

Genetics
General

Cite this

Alcalay, M., Zangrilli, D., Pandolfi, P. P., Longo, L., Mencarelli, A., Giacomucci, A., Rocchi, M., Biondi, A., Rambaldi, A., Lo Coco, F., Diverio, D., Donti, E., Grignani, F., & Pelicci, P. G. (1991). Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor α locus. Proceedings of the National Academy of Sciences of the United States of America, 88(5), 1977-1981.

Alcalay, M, Zangrilli, D, Pandolfi, PP, Longo, L, Mencarelli, A, Giacomucci, A, Rocchi, M, Biondi, A, Rambaldi, A, Lo Coco, F, Diverio, D, Donti, E, Grignani, F & Pelicci, PG 1991, 'Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor α locus', Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 5, pp. 1977-1981.

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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.",

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author = "M. Alcalay and D. Zangrilli and Pandolfi, {P. P.} and L. Longo and A. Mencarelli and A. Giacomucci and M. Rocchi and A. Biondi and A. Rambaldi and {Lo Coco}, F. and D. Diverio and E. Donti and F. Grignani and Pelicci, {P. G.}",

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AU - Alcalay, M.

AU - Zangrilli, D.

AU - Pandolfi, P. P.

AU - Longo, L.

AU - Mencarelli, A.

AU - Giacomucci, A.

AU - Rocchi, M.

AU - Biondi, A.

AU - Rambaldi, A.

AU - Lo Coco, F.

AU - Diverio, D.

AU - Donti, E.

AU - Grignani, F.

AU - Pelicci, P. G.

PY - 1991

Y1 - 1991

N2 - 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.

AB - 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.

KW - leukemogenesis

KW - rearrangements

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VL - 88

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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

Abstract

Keywords

ASJC Scopus subject areas

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