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p53-binding protein 1 is fused to the platelet-derived growth factor receptor ? in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder

p53-binding protein 1 is fused to the platelet-derived growth factor receptor ? in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder
p53-binding protein 1 is fused to the platelet-derived growth factor receptor ? in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder
We describe the fusion of TP53BP1 to PDGFRB in a patient with a chronic myeloid leukemia-like disorder associated with eosinophilia and a t(5;15)(q33;q22). TP53BP1 encodes 53BP1, a p53-binding protein that plays a role in cellular responses to DNA damage. The 53BP1-PDGFRß fusion protein is predicted to retain the kinetochore-binding domain of 53BP1 fused to the transmembrane and intracellular tyrosine kinase domain of PDGFRß. The presence of the fusion was confirmed by two-color fluorescence in situ hybridization, reverse transcription-PCR, and by characterizing the genomic breakpoints. The reciprocal fusion, which would contain the p53-binding 53BP1 BRCA1 COOH-terminal domains, was not detectable by fluorescence in situ hybridization or nested PCR. Imatinib, a known inhibitor of PDGFRß, blocked the growth of patient colony-forming unit, granulocyte-macrophage in vitro and produced a clinically significant response before relapse and subsequent death with imatinib-resistant disease. We conclude that TP53BP1-PDGFRB is a novel imatinib target in atypical chronic myeloid leukemia.

0008-5472
7216-7219
Grand, Francis H.
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Burgstaller, Sonja
b41f55fc-92c3-4eff-9b02-0244bf857e42
Kuhr, Thomas
f1f2c704-b57f-4449-bbf6-e0c16f0f99ef
Baxter, E. Joanna
09ded1f3-0305-4928-96de-6b565e9bf61b
Webersinke, Gerald
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Thaler, Josef
b9c9755c-f1b4-4599-985d-943e17fe2071
Chase, Andrew J.
a40a09c2-3073-4655-ba0b-a802e34914b5
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Grand, Francis H.
89bd846f-638a-4bda-b8a9-8a1989021b31
Burgstaller, Sonja
b41f55fc-92c3-4eff-9b02-0244bf857e42
Kuhr, Thomas
f1f2c704-b57f-4449-bbf6-e0c16f0f99ef
Baxter, E. Joanna
09ded1f3-0305-4928-96de-6b565e9bf61b
Webersinke, Gerald
63b585ec-8ac0-4409-a816-5824a66db40a
Thaler, Josef
b9c9755c-f1b4-4599-985d-943e17fe2071
Chase, Andrew J.
a40a09c2-3073-4655-ba0b-a802e34914b5
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4

Grand, Francis H., Burgstaller, Sonja, Kuhr, Thomas, Baxter, E. Joanna, Webersinke, Gerald, Thaler, Josef, Chase, Andrew J. and Cross, Nicholas C.P. (2004) p53-binding protein 1 is fused to the platelet-derived growth factor receptor ? in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder. Cancer Research, 64 (20), 7216-7219. (doi:10.1158/0008-5472.CAN-04-2005).

Record type: Article

Abstract

We describe the fusion of TP53BP1 to PDGFRB in a patient with a chronic myeloid leukemia-like disorder associated with eosinophilia and a t(5;15)(q33;q22). TP53BP1 encodes 53BP1, a p53-binding protein that plays a role in cellular responses to DNA damage. The 53BP1-PDGFRß fusion protein is predicted to retain the kinetochore-binding domain of 53BP1 fused to the transmembrane and intracellular tyrosine kinase domain of PDGFRß. The presence of the fusion was confirmed by two-color fluorescence in situ hybridization, reverse transcription-PCR, and by characterizing the genomic breakpoints. The reciprocal fusion, which would contain the p53-binding 53BP1 BRCA1 COOH-terminal domains, was not detectable by fluorescence in situ hybridization or nested PCR. Imatinib, a known inhibitor of PDGFRß, blocked the growth of patient colony-forming unit, granulocyte-macrophage in vitro and produced a clinically significant response before relapse and subsequent death with imatinib-resistant disease. We conclude that TP53BP1-PDGFRB is a novel imatinib target in atypical chronic myeloid leukemia.

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Published date: 2004

Identifiers

Local EPrints ID: 24726
URI: http://eprints.soton.ac.uk/id/eprint/24726
ISSN: 0008-5472
PURE UUID: d1b7732d-3f20-491f-b4f9-f5050dea063a
ORCID for Andrew J. Chase: ORCID iD orcid.org/0000-0001-6617-9953
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 03 Apr 2006
Last modified: 16 Mar 2024 03:23

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Contributors

Author: Francis H. Grand
Author: Sonja Burgstaller
Author: Thomas Kuhr
Author: E. Joanna Baxter
Author: Gerald Webersinke
Author: Josef Thaler
Author: Andrew J. Chase ORCID iD

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