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ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial

ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial
ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial
ATM mutation and BIRC3 deletion and/or mutation have independently been shown to have prognostic significance in chronic lymphocytic leukemia. However, the relative clinical importance of these abnormalities in patients with a deletion of 11q encompassing the ATM gene has not been established. We screened a cohort of 166 patients enriched for 11q-deletions for ATM mutations and BIRC3 deletion and mutation and determined the overall and progression-free survival among the 133 of these cases treated within the UK LRF CLL4 trial. SNP6.0 profiling demonstrated that BIRC3 deletion occurred in 83% of 11q-deleted cases and always co-existed with ATM deletion. For the first time we have demonstrated that 40% of BIRC3-deleted cases have concomitant deletion and mutation of ATM. While BIRC3 mutations were rare, they exclusively occurred with BIRC3 deletion and a wild-type residual ATM allele. In 11q-deleted cases, we confirmed that ATM mutation was associated with a reduced overall and progression-free survival comparable to that seen with TP53 abnormalities, whereas BIRC3 deletion and/or mutation had no impact on overall and progression-free survival. In conclusion, in 11q-deleted patients treated with first-line chemotherapy, ATM mutation rather than BIRC3 deletion and/or mutation identifies a subgroup with a poorer outcome
0390-6078
736-742
Rose-Zerilli, Matthew J.
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Forster, Jade
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Parker, Helen
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Parker, Anton
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Rodríguez, Ana E.
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Chaplin, Tracy
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Gardiner, Anne
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Steele, Andrew J.
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Collins, A.
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Young, Bryan D.
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Skowronska, Anna
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Catovsky, Daniel
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Stankovic, Tanja
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Oscier, D.G.
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Strefford, Jonathan C.
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Rose-Zerilli, Matthew J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Forster, Jade
de3b2ca3-6775-4bc8-a2f6-239499257160
Parker, Helen
33e0cd81-d45f-49bc-9539-09345d79d895
Parker, Anton
31389ac7-a2e6-4db1-989d-9551580fae35
Rodríguez, Ana E.
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Chaplin, Tracy
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Gardiner, Anne
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Steele, Andrew J.
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Collins, A.
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Young, Bryan D.
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Skowronska, Anna
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Catovsky, Daniel
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Stankovic, Tanja
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Oscier, D.G.
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Strefford, Jonathan C.
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Rose-Zerilli, Matthew J., Forster, Jade, Parker, Helen, Parker, Anton, Rodríguez, Ana E., Chaplin, Tracy, Gardiner, Anne, Steele, Andrew J., Collins, A., Young, Bryan D., Skowronska, Anna, Catovsky, Daniel, Stankovic, Tanja, Oscier, D.G. and Strefford, Jonathan C. (2014) ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial. Haematologica, 99 (4), 736-742. (doi:10.3324/haematol.2013.098574). (PMID:24584352)

Record type: Article

Abstract

ATM mutation and BIRC3 deletion and/or mutation have independently been shown to have prognostic significance in chronic lymphocytic leukemia. However, the relative clinical importance of these abnormalities in patients with a deletion of 11q encompassing the ATM gene has not been established. We screened a cohort of 166 patients enriched for 11q-deletions for ATM mutations and BIRC3 deletion and mutation and determined the overall and progression-free survival among the 133 of these cases treated within the UK LRF CLL4 trial. SNP6.0 profiling demonstrated that BIRC3 deletion occurred in 83% of 11q-deleted cases and always co-existed with ATM deletion. For the first time we have demonstrated that 40% of BIRC3-deleted cases have concomitant deletion and mutation of ATM. While BIRC3 mutations were rare, they exclusively occurred with BIRC3 deletion and a wild-type residual ATM allele. In 11q-deleted cases, we confirmed that ATM mutation was associated with a reduced overall and progression-free survival comparable to that seen with TP53 abnormalities, whereas BIRC3 deletion and/or mutation had no impact on overall and progression-free survival. In conclusion, in 11q-deleted patients treated with first-line chemotherapy, ATM mutation rather than BIRC3 deletion and/or mutation identifies a subgroup with a poorer outcome

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e-pub ahead of print date: 28 February 2014
Published date: 28 February 2014
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 364484
URI: http://eprints.soton.ac.uk/id/eprint/364484
ISSN: 0390-6078
PURE UUID: 72d29df9-1727-4e9d-ad65-25fa65bd9c93
ORCID for Matthew J. Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for Helen Parker: ORCID iD orcid.org/0000-0001-8308-9781
ORCID for Andrew J. Steele: ORCID iD orcid.org/0000-0003-0667-1596
ORCID for A. Collins: ORCID iD orcid.org/0000-0001-7108-0771
ORCID for Jonathan C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881

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Date deposited: 01 May 2014 12:19
Last modified: 21 Nov 2021 03:04

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Contributors

Author: Jade Forster
Author: Helen Parker ORCID iD
Author: Anton Parker
Author: Ana E. Rodríguez
Author: Tracy Chaplin
Author: Anne Gardiner
Author: A. Collins ORCID iD
Author: Bryan D. Young
Author: Anna Skowronska
Author: Daniel Catovsky
Author: Tanja Stankovic
Author: D.G. Oscier

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