Molecular analysis of simple variant translocations in acute promyelocytic leukemia
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1108702
- author
- Borrow, Julian ; Shipley, Janet ; Howe, Kathy ; Kiely, Fiona ; Goddard, Audrey ; Sheer, Denise ; Srivastava, Arun ; Antony, Astok C ; Fioretos, Thoas LU and Mitelman, Felix
- organization
- publishing date
- 1994
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Genes, Chromosomes and Cancer
- volume
- 9
- issue
- 4
- pages
- 234 - 243
- publisher
- John Wiley & Sons Inc.
- 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
- 2016-04-01 12:24:15
- date last changed
- 2021-09-19 03:11:45
@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 Inc.}},
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}},
doi = {{10.1002/gcc.2870090403}},
volume = {{9}},
year = {{1994}},
}