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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.
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NEOPLASIA Brief report
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 Foà,
Cesare Peschle, and
Arthur E. Frankel
From the Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità; Hematology, Department of Cellular Biotechnologies and Hematology, University "La Sapienza," and the Department of Biopathology, University of Tor Vergata, Rome, Italy; and the Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
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 patients with AML 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 2 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. (Blood. 2005;106:2527-2529)

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