SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-04-1150. This Article Full Text (PDF) All Versions of this Article: 2003-04-1150v1 102/12/4187    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wilkinson, K. Articles by Aguiar, R. C Search for Related Content PubMed PubMed Citation Articles by Wilkinson, K. Articles by Aguiar, R. C Social Bookmarking                   What's this? Submitted April 14, 2003 Accepted July 31, 2003 Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib Kathryn Wilkinson, Elvira R Velloso, Luiz F Lopes, Charles Lee, Jon C Aster, Margaret A Shipp, and Ricardo C Aguiar* Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA, USA Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA Department of Hematology, Hospital das Clinicas University of Sao Paulo, Sao Paulo, Brazil Department of Pediatrics, Hospital AC Camargo, Sao Paulo, Brazil * Corresponding author; email: Ricardo_Aguiar{at}dfci.harvard.edu. Eosinophilia is common in myeloproliferative disorders (MPD) with abnormalities of chromosome band 5q31-33, including those that present with t(1;5)(q23;q33). With the development of rational drug therapy, characterization of the molecular targets for these translocations could guide treatment and impact on patient survival. We cloned the t(1;5)(q23;q33) and showed that it fuses PDGFRB to the coiled-coil domains of a novel partner protein, Myomegalin. Using two-color interphase FISH, we also demonstrated that the eosinophils are clonal in these disorders. Imatinib mesylate has recently been shown to be efficacious in MPDs with PDGFR activation. Therefore, following our molecular studies, we were able to redirect this patient's treatment. Although she had refractory and progressive disease, once imatinib was started complete clinical and hematological remission, and major cytogenetic response was achieved. Given the therapeutic implications, our findings stress the need to aggressively investigate the molecular basis of these diseases, with emphasis on the PDGFR family. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Vannucchi, P. Guglielmelli, and A. Tefferi Advances in Understanding and Management of Myeloproliferative Neoplasms CA Cancer J Clin, May 1, 2009; 59(3): 171 - 191. [Abstract] [Full Text] [PDF] S. Fletcher and B. Bain Eosinophilic leukaemia Br. Med. Bull., April 18, 2007; (2007) ldm008v1. [Abstract] [Full Text] [PDF] C. Walz, G. Metzgeroth, C. Haferlach, A. Schmitt-Graeff, A. Fabarius, V. Hagen, O. Prummer, S. Rauh, R. Hehlmann, A. Hochhaus, et al. Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor {beta} gene Haematologica, February 1, 2007; 92(2): 163 - 169. [Abstract] [Full Text] [PDF] M. David, N. C. P. Cross, S. Burgstaller, A. Chase, C. Curtis, R. Dang, M. Gardembas, J. M. Goldman, F. Grand, G. Hughes, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders Blood, January 1, 2007; 109(1): 61 - 64. [Abstract] [Full Text] [PDF] R. H. Alvarez, H. M. Kantarjian, and J. E. Cortes Biology of Platelet-Derived Growth Factor and Its Involvement in Disease Mayo Clin. Proc., September 1, 2006; 81(9): 1241 - 1257. [Abstract] [Full Text] [PDF] A. Tefferi, M. A. Elliott, and A. Pardanani Atypical Myeloproliferative Disorders: Diagnosis and Management Mayo Clin. Proc., April 1, 2006; 81(4): 553 - 563. [Abstract] [Full Text] [PDF] S. Frohling, C. Scholl, D. G. Gilliland, and R. L. Levine Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications J. Clin. Oncol., September 10, 2005; 23(26): 6285 - 6295. [Abstract] [Full Text] [PDF] B. Delaval, S. Letard, H. Lelievre, V. Chevrier, L. Daviet, P. Dubreuil, and D. Birnbaum Oncogenic Tyrosine Kinase of Malignant Hemopathy Targets the Centrosome Cancer Res., August 15, 2005; 65(16): 7231 - 7240. [Abstract] [Full Text] [PDF] A. Tefferi and D. G. Gilliland The JAK2V617F Tyrosine Kinase Mutation in Myeloproliferative Disorders: Status Report and Immediate Implications for Disease Classification and Diagnosis Mayo Clin. Proc., July 1, 2005; 80(7): 947 - 958. [Abstract] [PDF] A. Tefferi Blood Eosinophilia: A New Paradigm in Disease Classification, Diagnosis, and Treatment Mayo Clin. Proc., January 1, 2005; 80(1): 75 - 83. [Abstract] [PDF] M. Wadleigh, D. J. DeAngelo, J. D. Griffin, and R. M. Stone After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies Blood, January 1, 2005; 105(1): 22 - 30. [Abstract] [Full Text] [PDF] F. H. Grand, S. Burgstaller, T. Kuhr, E. J. Baxter, G. Webersinke, J. Thaler, A. J. Chase, and N. C. P. Cross p53-Binding Protein 1 Is Fused to the Platelet-Derived Growth Factor Receptor {beta} in a Patient with a t(5;15)(q33;q22) and an Imatinib-Responsive Eosinophilic Myeloproliferative Disorder Cancer Res., October 15, 2004; 64(20): 7216 - 7219. [Abstract] [Full Text] [PDF] A. Pardanani and A. Tefferi Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders Blood, October 1, 2004; 104(7): 1931 - 1939. [Abstract] [Full Text] [PDF] C. Morerio, M. Acquila, C. Rosanda, A. Rapella, C. Dufour, F. Locatelli, E. Maserati, F. Pasquali, and C. Panarello HCMOGT-1 Is a Novel Fusion Partner to PDGFRB in Juvenile Myelomonocytic Leukemia with t(5;17)(q33;p11.2) Cancer Res., April 15, 2004; 64(8): 2649 - 2651. [Abstract] [Full Text] [PDF] J. L. Vizmanos, F. J. Novo, J. P. Roman, E. J. Baxter, I. Lahortiga, M. J. Larrayoz, M. D. Odero, P. Giraldo, M. J. Calasanz, and N. C. P. Cross NIN, a Gene Encoding a CEP110-Like Centrosomal Protein, Is Fused to PDGFRB in a Patient with a t(5;14)(q33;q24) and an Imatinib-Responsive Myeloproliferative Disorder1 Cancer Res., April 15, 2004; 64(8): 2673 - 2676. [Abstract] [Full Text] [PDF] J. Gotlib, J. Cools, J. M. Malone III, S. L. Schrier, D. G. Gilliland, and S. E. Coutre The FIP1L1-PDGFR{alpha} fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management Blood, April 15, 2004; 103(8): 2879 - 2891. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020