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Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta

Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta
Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta
Background A small proportion of patients with chronic myeloproliferative diseases have constitutive activation of the gene for platelet-derived growth factor receptor beta (PDGFRB), which encodes a receptor tyrosine kinase. The gene is located on chromosome 5q33, and the activation is usually caused by a t(5;12)(q33;p13) translocation associated with an ETV6-PDGFRB fusion gene. The tyrosine kinase inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and KIT kinases and has impressive clinical efficacy in BCR-ABL–positive chronic myeloid leukemia.
Methods We treated four patients who had chronic myeloproliferative diseases and chromosomal translocations involving 5q33 with imatinib mesylate (400 mg daily). Three of the four patients presented with leukocytosis and eosinophilia; their leukemia cells carried the ETV6-PDGFRB fusion gene. The fourth patient had leukocytosis, eosinophilia, and a t(5;12) translocation involving PDGFRB and an unknown partner gene; he also had extensive raised, ulcerated skin lesions that had been present for a long time.
Results In all four patients, a normal blood count was achieved within four weeks after treatment began. In the patient with skin disease, the lesions began to resolve shortly after treatment began. The t(5;12) translocation was undetectable by 12 weeks in three patients and by 36 weeks in the fourth patient. In the three patients with the ETV6-PDGFRB fusion gene, the transcript level decreased, and in one patient, it became undetectable by 36 weeks. All responses were durable at 9 to 12 months of follow-up.
Conclusions Imatinib mesylate induces durable responses in patients with chronic myeloproliferative diseases associated with activation of PDGFRB.
481-487
Apperley, Jane F.
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Gardembas, Martine
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Melo, Junia V.
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Russell-Jones, Robin
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Bain, Barbara J.
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Baxter, E. Joanna
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Chase, Andrew
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Chessells, Judith M.
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Colombat, Marie
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Dearden, Claire E.
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Dimitrijevic, Sandra
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Mahon, Francois X.
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Marin, David
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Nikolova, Zariana
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Olavarria, Eduardo
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Silberman, Sandra
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Schultheis, Beate
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Cross, Nicholas C.P.
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Goldman, John M.
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Apperley, Jane F.
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Gardembas, Martine
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Melo, Junia V.
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Russell-Jones, Robin
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Bain, Barbara J.
96de5333-b51f-41db-86ba-1e5073868f93
Baxter, E. Joanna
09ded1f3-0305-4928-96de-6b565e9bf61b
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
Chessells, Judith M.
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Colombat, Marie
7a28cd1d-6062-49d3-a009-412d33626502
Dearden, Claire E.
7bf313f7-6e4e-4660-a1a1-65cfd21afb9f
Dimitrijevic, Sandra
01c5b093-7705-4bce-9b3f-bfa28b139a51
Mahon, Francois X.
ecd1e479-605a-415e-bf53-4b4788206471
Marin, David
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Nikolova, Zariana
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Olavarria, Eduardo
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Silberman, Sandra
79369c31-86ad-4904-91ac-20905697b47a
Schultheis, Beate
81cee7d3-02b3-4a0d-9743-782e3654a3f4
Cross, Nicholas C.P.
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Goldman, John M.
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Apperley, Jane F., Gardembas, Martine, Melo, Junia V., Russell-Jones, Robin, Bain, Barbara J., Baxter, E. Joanna, Chase, Andrew, Chessells, Judith M., Colombat, Marie, Dearden, Claire E., Dimitrijevic, Sandra, Mahon, Francois X., Marin, David, Nikolova, Zariana, Olavarria, Eduardo, Silberman, Sandra, Schultheis, Beate, Cross, Nicholas C.P. and Goldman, John M. (2002) Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. New England Journal of Medicine, 347 (7), 481-487. (doi:10.1056/NEJMoa020150).

Record type: Article

Abstract

Background A small proportion of patients with chronic myeloproliferative diseases have constitutive activation of the gene for platelet-derived growth factor receptor beta (PDGFRB), which encodes a receptor tyrosine kinase. The gene is located on chromosome 5q33, and the activation is usually caused by a t(5;12)(q33;p13) translocation associated with an ETV6-PDGFRB fusion gene. The tyrosine kinase inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and KIT kinases and has impressive clinical efficacy in BCR-ABL–positive chronic myeloid leukemia.
Methods We treated four patients who had chronic myeloproliferative diseases and chromosomal translocations involving 5q33 with imatinib mesylate (400 mg daily). Three of the four patients presented with leukocytosis and eosinophilia; their leukemia cells carried the ETV6-PDGFRB fusion gene. The fourth patient had leukocytosis, eosinophilia, and a t(5;12) translocation involving PDGFRB and an unknown partner gene; he also had extensive raised, ulcerated skin lesions that had been present for a long time.
Results In all four patients, a normal blood count was achieved within four weeks after treatment began. In the patient with skin disease, the lesions began to resolve shortly after treatment began. The t(5;12) translocation was undetectable by 12 weeks in three patients and by 36 weeks in the fourth patient. In the three patients with the ETV6-PDGFRB fusion gene, the transcript level decreased, and in one patient, it became undetectable by 36 weeks. All responses were durable at 9 to 12 months of follow-up.
Conclusions Imatinib mesylate induces durable responses in patients with chronic myeloproliferative diseases associated with activation of PDGFRB.

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Published date: 15 August 2002

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Local EPrints ID: 24612
URI: http://eprints.soton.ac.uk/id/eprint/24612
PURE UUID: 84738f65-1070-442f-a024-68727a5fbab8
ORCID for Andrew 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: 18 Feb 2021 16:59

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Contributors

Author: Jane F. Apperley
Author: Martine Gardembas
Author: Junia V. Melo
Author: Robin Russell-Jones
Author: Barbara J. Bain
Author: E. Joanna Baxter
Author: Andrew Chase ORCID iD
Author: Judith M. Chessells
Author: Marie Colombat
Author: Claire E. Dearden
Author: Sandra Dimitrijevic
Author: Francois X. Mahon
Author: David Marin
Author: Zariana Nikolova
Author: Eduardo Olavarria
Author: Sandra Silberman
Author: Beate Schultheis
Author: John M. Goldman

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