• Jane F Apperley, Martine Gardembas, Junia V Melo, Robin Russell-Jones, Barbara J Bain, E Joanna Baxter, Andrew Chase, Judith M Chessells, Marie Colombat, Claire E Dearden, Sasa Dimitrijevic, François-X Mahon, David Marin, Zariana Nikolova, Eduardo Olavarria, Sandra Silberman, Beate Schultheis, Nicholas C P Cross, and John M Goldman.
• Department of Haematology, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom. j.apperley@ic.ac.uk
• N. Engl. J. Med. 2002 Aug 15; 347 (7): 481487481-7.

BackgroundA 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.MethodsWe 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.ResultsIn 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.ConclusionsImatinib mesylate induces durable responses in patients with chronic myeloproliferative diseases associated with activation of PDGFRB.Copyright 2002 Massachusetts Medical Society

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