Response to Imatinib Mesylate in Patients with Chronic Myeloproliferative Diseases with Rearrangements of the Platelet-Derived Growth Factor Receptor Beta

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; Dimitrijevic, S.; Mahon, François Xavier; Marín, David; Nikolova, Zariana; Olavarría, Eduardo; Silberman, Sandra; Schultheis, Beate; Cross, Nicholas C. P.; Goldman, John M.

doi:10.1056/nejmoa020150

Cited by 582 publications

(355 citation statements)

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“…Patients with these fusion genes have been reported to achieve rapid hematologic, cytogenetic, and molecular responses with imatinib therapy. 40,41 However, none of our patients had any abnormality involving chromosome 5q33 and none had eosinophilia, a common feature among patients with these fusion genes. Similar results were reported by Raza et al 42 in patients without PDGF-R fusion genes.…”

Section: Discussionmentioning

confidence: 63%

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high‐risk myelodysplastic syndrome, and myeloproliferative disorders

Cortes

Giles

O’Brien

et al. 2003

Cancer

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BACKGROUNDImatinib mesylate is a selective tyrosine kinase inhibitor of c‐abl, bcr/abl, c‐kit, and platelet‐derived growth factor‐receptor (PDGF‐R). c‐kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD).METHODSThe authors investigated the efficacy of imatinib in patients with these disorders. Forty‐eight patients with AML (n = 10), MDS (n = 8), myelofibrosis (n = 18), atypical chronic myeloid leukemia (CML; n = 7), chronic myelomonocytic leukemia (CMML; n = 3), or polycythemia vera (n = 2) were treated with imatinib 400 mg daily.RESULTSNone of the patients with AML or MDS responded. Among patients with myelofibrosis, 10 of 14 patients with splenomegaly (71%) had a 30% or greater reduction in spleen size, 1 patient had trilineage hematologic improvement, 2 had erythroid hematologic improvement, and 1 had improvement in platelet count. One patient with atypical CML had erythroid hematologic improvement. Both patients with polycythemia vera needed fewer phlebotomies (from 2–3 per year to none during the 8 months of therapy and from 3–6 per year to 1 during 9 months of therapy). None of the three patients with CMML responded. Treatment was well tolerated. The side effects were similar to those observed in patients with CML.CONCLUSIONSWithin these small subgroups of disease types, single‐agent imatinib did not achieve a significant clinical response among patients with AML, MDS, atypical CML, or CMML without PDGF‐R fusion genes. Preliminary data on polycythemia vera are promising and deserve further investigation. Responses among myelofibrosis patients were minor. Therefore, a combination treatment regimen including imatinib may be more effective. Cancer 2003;97:2760–6. © 2003 American Cancer Society.DOI 10.1002/cncr.0000

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Section: Discussionmentioning

confidence: 63%

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high‐risk myelodysplastic syndrome, and myeloproliferative disorders

Cortes

Giles

O’Brien

et al. 2003

Cancer

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“…Moreover, patients with myeloproliferative disorders carrying FIP1L1/PDGFRa and activated forms of PDGFRb were also successfully treated with IM (Apperley et al, 2002;Cools et al, 2003). In addition, IM was proven to be effective against cells transfected with TEL/ABL (Carroll et al, 1997).…”

Section: Facilitation Of Genomic Instabilitymentioning

confidence: 99%

Fusion tyrosine kinases: a result and cause of genomic instability

Penserga

Skórski

2006

Oncogene

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“…48 Other PDGFR␤ fusion partners also have been described, and it has been reported that imatinib is effective in some patients with these fusion genes. 49 2) The fusion gene FIP1L1-PDGFR␣ has been demonstrated in 9 of 16 (56%) patients with idiopathic hypereosinophilic syndrome (HES), leading to the constitutive activation of PDGFR␣ kinase in the neoplastic clone. In vitro studies of the effect of imatinib mesylate on the growth of Ba/F3 cells that expressed FIP1L1-PDGFR␣ showed that they were inhibited efficiently by much lower concentrations of imatinib than Ba/F3 cells that expressed BCR-ABL (50% inhibitory concentration, 3.2 nM vs. 582 nM, respectively).…”

Section: Constitutively Active Kinases As Targets Of Therapymentioning

confidence: 99%

New agents in acute myeloid leukemia and other myeloid disorders

Ravandi

Kantarjian

Giles

et al. 2004

Cancer

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Response to Imatinib Mesylate in Patients with Chronic Myeloproliferative Diseases with Rearrangements of the Platelet-Derived Growth Factor Receptor Beta

Abstract: Imatinib mesylate induces durable responses in patients with chronic myeloproliferative diseases associated with activation of PDGFRB.

Cited by 582 publications

References 22 publications

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high‐risk myelodysplastic syndrome, and myeloproliferative disorders

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high‐risk myelodysplastic syndrome, and myeloproliferative disorders

Fusion tyrosine kinases: a result and cause of genomic instability

New agents in acute myeloid leukemia and other myeloid disorders

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