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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2527-2529. Prepublished online as a Blood First Edition Paper on May 31, 2005; DOI 10.1182/blood-2005-02-0540. This Article Full Text (PDF) All Versions of this Article: 2005-02-0540v1 106/7/2527    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 Testa, U. Articles by Frankel, A. E Search for Related Content PubMed PubMed Citation Articles by Testa, U. Articles by Frankel, A. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2005 Accepted May 16, 2005 Diphtheria toxin fused to variant human interleukin-3 induces cytotoxicity of blasts from patients with acute myeloid leukemia according to the level of interleukin-3 receptor expression Ugo Testa*, Roberta Riccioni, Mauro Biffoni, Daniela Diverio, Francesco Lo-Coco, Robin Foa, Cesare Peschle, and Arthur E Frankel Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy Hematology, Department of Cellular Biotechnologies and Hematology, University "La Sapienza", Rome, Italy Department of Biopathology, University of Tor Vergata, Rome, Italy Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA * Corresponding author; email: u.testa{at}iss.it. Leukemic blasts from patients with acute myeloid leukemia (AML) frequently express high levels of the interleukin-3 receptor chain (IL-3R). In the present study, we have explored the sensitivity of primary leukemic blasts obtained from 34 AML patients to a diphtheria toxin (DT) composed of the catalytic and translocation domains of DT (DT388) fused to IL-3 (DT388IL-3) and to DT388 fused to a variant IL-3 with increased binding affinity (DT388IL-3[K116W]). On a molar basis, DT388IL-3[K116W] was significantly more active than DT388IL-3 in mediating leukemic cell killing. The rate of cell killing induced by the two DT/IL-3 fusion proteins was significantly correlated with the level of IL-3R/IL-3R expressed on leukemic blasts. These observations support a potential use of DT388IL-3[K116W] in the treatment of refractory AMLs and provide a simple biochemical parameter for the selection of eligible patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Djokic, E. Bjorklund, E. Blennow, J. Mazur, S. Soderhall, and A. Porwit Overexpression of CD123 correlates with the hyperdiploid genotype in acute lymphoblastic leukemia Haematologica, July 1, 2009; 94(7): 1016 - 1019. [Abstract] [Full Text] [PDF] J. Chen, J. Olsen, S. Ford, S. Mirza, A. Walker, J. M. Murphy, and I. G. Young A New Isoform of Interleukin-3 Receptor {alpha} with Novel Differentiation Activity and High Affinity Binding Mode J. Biol. Chem., February 27, 2009; 284(9): 5763 - 5773. [Abstract] [Full Text] [PDF] R. Singh, U. Samant, S. Hyland, P. R. Chaudhari, W. S. Wels, and D. Bandyopadhyay Target-specific cytotoxic activity of recombinant immunotoxin scFv(MUC1)-ETA on breast carcinoma cells and primary breast tumors Mol. Cancer Ther., February 1, 2007; 6(2): 562 - 569. [Abstract] [Full Text] [PDF] L. Yalcintepe, A. E. Frankel, and D. E. Hogge Expression of interleukin-3 receptor subunits on defined subpopulations of acute myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin-3 fusion protein against malignant progenitors that engraft in immunodeficient mice Blood, November 15, 2006; 108(10): 3530 - 3537. [Abstract] [Full Text] [PDF] D. E. Hogge, L. Yalcintepe, S.-H. Wong, B. Gerhard, and A. E. Frankel Variant Diphtheria Toxin-Interleukin-3 Fusion Proteins with Increased Receptor Affinity Have Enhanced Cytotoxicity against Acute Myeloid Leukemia Progenitors Clin. Cancer Res., February 15, 2006; 12(4): 1284 - 1291. [Abstract] [Full Text] [PDF]

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