Journal Article

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

Dearden, Claire E, Silberman, Sandra, Russell-Jones, Robin, Marin, David, Apperley, Jane F, Melo, Junia V, Nikolova, Zariana, Dimitrijevic, Sasa, Gardembas, Martine, Chase, Andrew, Baxter, E. Joanna, Cross, Nicholas C.P, Schultheis, Beate, Olavarria, Eduardo, Goldman, John M, Bain, Barbara J, Mahon, François-X, Chessells, Judith M, Colombat, Marie

2002

Overview

Imatinib mesylate blocks the activity of three protein tyrosine kinases: ABL, KIT, and platelet-derived growth factor receptor β (PDGFRB). These kinases have crucial roles in chronic myelogenous leukemia (ABL), gastrointestinal stromal tumors (KIT), and certain myeloproliferative diseases (PDGFRB). The first two types of neoplasms have been shown to respond to imatinib mesylate. This article reports that in four patients, a myeloproliferative disorder involving a rearranged PDGFRB gene also responded to the drug. The association of leukemia, eosinophilia, and abnormalities of chromosome 12p13 was originally reported by Keene et al. in 1987 1 ; two of the four patients included in that report also had translocations involving chromosome 5q3. Subsequently, Golub et al. 2 showed that the previously described t(5;12)(q31–q33;p13) chromosomal abnormality, characteristic of some cases of chronic myelomonocytic leukemia, was associated with a fusion gene linking TEL (now known as ETV6 ) with platelet-derived growth factor receptor beta ( PDGFRB ). At least 34 cases of chronic myeloproliferative disease associated with a t(5;12)(q31–q33;p13) translocation have now been reported, 3 and the PDGFRB gene is known . . .

• Publisher: Massachusetts Medical Society
• Subject: Adult / Aged / Antineoplastic agents / Benzamides / Binding sites / Biological and medical sciences / Bone marrow / Chemotherapy / Child / Chromosomes / Chromosomes, Human, Pair 5 / Chronic obstructive pulmonary disease, asthma / Disease / DNA-Binding Proteins - genetics / Drug therapy / Eosinophilia - drug therapy / ETS Translocation Variant 6 Protein / Gene Rearrangement / Humans / Imatinib Mesylate / In Situ Hybridization, Fluorescence / Leukemia / Leukocytosis - drug therapy / Male / Medical sciences / Middle Aged / Myeloproliferative Disorders - drug therapy / Myeloproliferative Disorders - genetics / Myeloproliferative Disorders - pathology / Oncogene Proteins, Fusion - genetics / Patients / Pharmacology. Drug treatments / Piperazines - therapeutic use / Pneumology / Protein-Tyrosine Kinases - antagonists & inhibitors / Proteins / Proto-Oncogene Proteins c-ets / Pyrimidines - therapeutic use / Receptor, Platelet-Derived Growth Factor beta - genetics / Repressor Proteins - genetics