Atypical mRNA fusions in PML-RARA positive, RARA-PML negative acute promyelocytic leukemia
Atypical mRNA fusions in PML-RARA positive, RARA-PML negative acute promyelocytic leukemia
Reciprocal RARA-PML transcripts are not detected in approximately 25% of patients with PML-RARA positive acute promyelocytic leukemia (APL), but the reasons for this are poorly understood. We studied 21 PML-RARA positive/RARA-PML negative cases by bubble PCR and multiplex long template PCR to identify the genomic breakpoints. Additional RT-PCR analysis was performed based on the DNA findings. Three cases were found to have complex rearrangements involving a third locus: the first had a PML-CDC6-RARA forward DNA fusion and expressed a chimeric PML-CDC6-RARA mRNA in addition to a PML-RARA. The other two had HERC1-PML and NT_009714.17-PML genomic fusion sequences at their respective reciprocal breakpoints. Six patients were falsely classified as RARA-PML negative due to deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical RARA-PML fusion transcripts, which were not identified by conventional RT-PCR assays. This study demonstrates that the frequency of RARA-PML expression has been underestimated and highlights remarkable complexity at chromosomal breakpoint regions in APL even in cases with an apparently simple balanced t(15;17)(q24;q12)
471-479
Walz, Christopher
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Grimwade, David
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Saussele, Susanne
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Lengfelder, Eva
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Haferlach, Claudia
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Schnittger, Susanne
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Lafage-Pochitaloff, Marina
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Hochhaus, Andreas
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Cross, Nicholas C.P.
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Reiter, Andreas
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May 2010
Walz, Christopher
a41e26c3-5f0f-45f3-b265-b044fd5b0d4b
Grimwade, David
9f299c71-1e4c-42b1-9b39-d1e1ddc1dc26
Saussele, Susanne
148d36ac-b14b-42ff-b4cc-17dbe7f720f7
Lengfelder, Eva
4e53c373-7238-4bdd-88e5-eb5b4dccc65b
Haferlach, Claudia
0bf0896a-7b9c-451a-9e64-935ecdd7aa15
Schnittger, Susanne
5157942c-96eb-47cd-9837-3feea8ec8984
Lafage-Pochitaloff, Marina
26af43da-edb3-4318-bc1a-4810a59fc039
Hochhaus, Andreas
b37b9b7d-85ff-455e-994d-fcc2adf94088
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
Walz, Christopher, Grimwade, David, Saussele, Susanne, Lengfelder, Eva, Haferlach, Claudia, Schnittger, Susanne, Lafage-Pochitaloff, Marina, Hochhaus, Andreas, Cross, Nicholas C.P. and Reiter, Andreas
(2010)
Atypical mRNA fusions in PML-RARA positive, RARA-PML negative acute promyelocytic leukemia.
Genes, Chromosomes and Cancer, 49 (5), .
(doi:10.1002/gcc.20757).
Abstract
Reciprocal RARA-PML transcripts are not detected in approximately 25% of patients with PML-RARA positive acute promyelocytic leukemia (APL), but the reasons for this are poorly understood. We studied 21 PML-RARA positive/RARA-PML negative cases by bubble PCR and multiplex long template PCR to identify the genomic breakpoints. Additional RT-PCR analysis was performed based on the DNA findings. Three cases were found to have complex rearrangements involving a third locus: the first had a PML-CDC6-RARA forward DNA fusion and expressed a chimeric PML-CDC6-RARA mRNA in addition to a PML-RARA. The other two had HERC1-PML and NT_009714.17-PML genomic fusion sequences at their respective reciprocal breakpoints. Six patients were falsely classified as RARA-PML negative due to deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical RARA-PML fusion transcripts, which were not identified by conventional RT-PCR assays. This study demonstrates that the frequency of RARA-PML expression has been underestimated and highlights remarkable complexity at chromosomal breakpoint regions in APL even in cases with an apparently simple balanced t(15;17)(q24;q12)
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Published date: May 2010
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Local EPrints ID: 72518
URI: http://eprints.soton.ac.uk/id/eprint/72518
ISSN: 1045-2257
PURE UUID: 46b96862-19ed-4bf9-a189-101cc05e3d65
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Date deposited: 17 Feb 2010
Last modified: 14 Mar 2024 02:46
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Author:
Christopher Walz
Author:
David Grimwade
Author:
Susanne Saussele
Author:
Eva Lengfelder
Author:
Claudia Haferlach
Author:
Susanne Schnittger
Author:
Marina Lafage-Pochitaloff
Author:
Andreas Hochhaus
Author:
Andreas Reiter
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