The New England journal of medicine · 2002
Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.
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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 Sasa, Mahon François-X, Marin David, Nikolova Zariana, Olavarria Eduardo, Silberman Sandra, Schultheis Beate, Cross Nicholas C P, Goldman John M
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAgedBenzamidesChildChromosomes, Human, Pair 5DNA-Binding ProteinsEosinophiliaGene RearrangementHumansImatinib MesylateIn Situ Hybridization, FluorescenceLeukocytosisMaleMiddle AgedMyeloproliferative DisordersOncogene Proteins, FusionPiperazinesProtein-Tyrosine KinasesProto-Oncogene Proteins c-etsPyrimidinesReceptor, Platelet-Derived Growth Factor betaRepressor ProteinsETS Translocation Variant 6 Protein