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Molecular analysis of simple variant translocations in acute promyelocytic leukemia

Borrow, Julian; Shipley, Janet; Howe, Kathy; Kiely, Fiona; Goddard, Audrey; Sheer, Denise; Srivastava, Arun; Antony, Astok C; Fioretos, Thoas LU and Mitelman, Felix (1994) In Genes, Chromosomes and Cancer 9(4). p.234-243
Abstract
The primary cytogenetic abnormality in acute promyelocytic leukemia (APL; FAB M3) is a reciprocal translocation, t(15;17)(q22;q12), which serves to fuse the PML gene on chromosome 15 to the retinoic acid receptor alpha (RARA) gene on chromosome 17. A PML-RARA fusion message transcribed from the der(15) is thought to mediate leukemogenesis. Two APL patients with simple variants of this translocation, t(3;15)(q21;q22) and t(X;15)(p11;q22), have previously been reported who lack cytogenetic involvement of chromosome 17, although their breakpoint positions on chromosome 15 still suggest the involvement of the PML gene. Here we report on a combined analysis by molecular genetics and in situ hybridization of these two patients, in which we... (More)
The primary cytogenetic abnormality in acute promyelocytic leukemia (APL; FAB M3) is a reciprocal translocation, t(15;17)(q22;q12), which serves to fuse the PML gene on chromosome 15 to the retinoic acid receptor alpha (RARA) gene on chromosome 17. A PML-RARA fusion message transcribed from the der(15) is thought to mediate leukemogenesis. Two APL patients with simple variants of this translocation, t(3;15)(q21;q22) and t(X;15)(p11;q22), have previously been reported who lack cytogenetic involvement of chromosome 17, although their breakpoint positions on chromosome 15 still suggest the involvement of the PML gene. Here we report on a combined analysis by molecular genetics and in situ hybridization of these two patients, in which we wanted to determine whether the PML gene has alternative fusion partners or whether cryptic rearrangement of the RARA locus has occurred instead. A cryptic involvement of RARA was demonstrated in both patients by a combination of Southern analysis, reverse transcription coupled to PCR (RT-PCR), and fluorescence in situ hybridization. The results indicate an absolute requirement for the rearrangement of the RARA gene in the pathogenesis of APL and underline the importance of RARA during normal myeloid differentiation. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
9
issue
4
pages
234 - 243
publisher
John Wiley & Sons
external identifiers
  • pmid:7519045
  • scopus:0028258276
ISSN
1045-2257
DOI
10.1002/gcc.2870090403
language
English
LU publication?
yes
id
d46fcb91-48f1-4ed9-b427-15d6791cfc0a (old id 1108702)
date added to LUP
2008-07-24 15:30:33
date last changed
2017-04-30 09:29:14
@article{d46fcb91-48f1-4ed9-b427-15d6791cfc0a,
  abstract     = {The primary cytogenetic abnormality in acute promyelocytic leukemia (APL; FAB M3) is a reciprocal translocation, t(15;17)(q22;q12), which serves to fuse the PML gene on chromosome 15 to the retinoic acid receptor alpha (RARA) gene on chromosome 17. A PML-RARA fusion message transcribed from the der(15) is thought to mediate leukemogenesis. Two APL patients with simple variants of this translocation, t(3;15)(q21;q22) and t(X;15)(p11;q22), have previously been reported who lack cytogenetic involvement of chromosome 17, although their breakpoint positions on chromosome 15 still suggest the involvement of the PML gene. Here we report on a combined analysis by molecular genetics and in situ hybridization of these two patients, in which we wanted to determine whether the PML gene has alternative fusion partners or whether cryptic rearrangement of the RARA locus has occurred instead. A cryptic involvement of RARA was demonstrated in both patients by a combination of Southern analysis, reverse transcription coupled to PCR (RT-PCR), and fluorescence in situ hybridization. The results indicate an absolute requirement for the rearrangement of the RARA gene in the pathogenesis of APL and underline the importance of RARA during normal myeloid differentiation.},
  author       = {Borrow, Julian and Shipley, Janet and Howe, Kathy and Kiely, Fiona and Goddard, Audrey and Sheer, Denise and Srivastava, Arun and Antony, Astok C and Fioretos, Thoas and Mitelman, Felix},
  issn         = {1045-2257},
  language     = {eng},
  number       = {4},
  pages        = {234--243},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Molecular analysis of simple variant translocations in acute promyelocytic leukemia},
  url          = {http://dx.doi.org/10.1002/gcc.2870090403},
  volume       = {9},
  year         = {1994},
}