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Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome

Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome
Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome
The 8p11 myeloproliferative syndrome is a rare, aggressive myeloproliferative neoplasm characterised by constitutively active FGFR1 fusion proteins that arise from specific
chromosomal translocations and which drive aberrant proliferation. Although FGFR1 inhibitors have shown in vitro activity against FGFR1 fusions, none are in use clinically and there is a need to assess additional compounds as potential therapy. Here we use cell lines
and primary cells to investigate ponatinib (AP24534). Ponatinib-treated Ba/F3 cells transformed by ZMYM2-FGFR1 and BCR-FGFR1 and the FGFR1OP2-FGFR1 positive
KG1A cell line showed reduced proliferation and decreased survival when compared to control cells. Inhibition induced apoptosis and reduced phosphorylation of the FGFR1 fusion
proteins and substrates. Ponatinib-treated cells from five 8p11 myeloproliferative syndrome patients showed reduced colony growth compared to controls. In one evaluable patient, ponatinib specifically reduced numbers of FGFR1-fusion gene positive colonies. Ponatinib therefore shows considerable promise for the treatment of patients with 8p11
myeloproliferative syndrome.
0390-6078
103-106
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
Bryant, Catherine
d53ab6c9-909d-43cb-84fc-3e197df377f3
Score, Joannah
ea0db6ef-c17e-4915-b216-ac67c07b26b7
Cross, Nicholas C. P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
Bryant, Catherine
d53ab6c9-909d-43cb-84fc-3e197df377f3
Score, Joannah
ea0db6ef-c17e-4915-b216-ac67c07b26b7
Cross, Nicholas C. P.
f87650da-b908-4a34-b31b-d62c5f186fe4

Chase, Andrew, Bryant, Catherine, Score, Joannah and Cross, Nicholas C. P. (2013) Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome. Haematologica, 98 (1), 103-106. (doi:10.3324/haematol.2012.066407). (PMID:22875613)

Record type: Article

Abstract

The 8p11 myeloproliferative syndrome is a rare, aggressive myeloproliferative neoplasm characterised by constitutively active FGFR1 fusion proteins that arise from specific
chromosomal translocations and which drive aberrant proliferation. Although FGFR1 inhibitors have shown in vitro activity against FGFR1 fusions, none are in use clinically and there is a need to assess additional compounds as potential therapy. Here we use cell lines
and primary cells to investigate ponatinib (AP24534). Ponatinib-treated Ba/F3 cells transformed by ZMYM2-FGFR1 and BCR-FGFR1 and the FGFR1OP2-FGFR1 positive
KG1A cell line showed reduced proliferation and decreased survival when compared to control cells. Inhibition induced apoptosis and reduced phosphorylation of the FGFR1 fusion
proteins and substrates. Ponatinib-treated cells from five 8p11 myeloproliferative syndrome patients showed reduced colony growth compared to controls. In one evaluable patient, ponatinib specifically reduced numbers of FGFR1-fusion gene positive colonies. Ponatinib therefore shows considerable promise for the treatment of patients with 8p11
myeloproliferative syndrome.

Full text not available from this repository.

More information

e-pub ahead of print date: 8 August 2012
Published date: January 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 342166
URI: https://eprints.soton.ac.uk/id/eprint/342166
ISSN: 0390-6078
PURE UUID: 05e3994f-2f45-4083-8469-9ad40d0926f6
ORCID for Nicholas C. P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 14 Aug 2012 09:07
Last modified: 17 Jul 2019 00:59

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