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, Arthur E. Frankel

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Leukemic blasts from patients with acute myeloid leukemia (AML) frequently express high levels of the interleukin-3 receptor α chain (IL-3Rα). 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 DT 388IL-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-3Rα/IL-3Rβ 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.

Original languageEnglish (US)
Pages (from-to)2527-2529
Number of pages3
JournalBlood
Volume106
Issue number7
DOIs
StatePublished - Oct 2005

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Interleukin-3 Receptors
Diphtheria Toxin
Interleukin-3
Cytotoxicity
Acute Myeloid Leukemia
Cells
Refractory materials
Patient Selection
Catalytic Domain
Fusion reactions

ASJC Scopus subject areas

  • Hematology

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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. / Testa, Ugo; Riccioni, Roberta; Biffoni, Mauro; Diverio, Daniela; Lo-Coco, Francesco; Foà, Robin; Peschle, Cesare; Frankel, Arthur E.

In: Blood, Vol. 106, No. 7, 10.2005, p. 2527-2529.

Research output: Contribution to journalArticle

Testa, Ugo ; Riccioni, Roberta ; Biffoni, Mauro ; Diverio, Daniela ; Lo-Coco, Francesco ; Foà, Robin ; Peschle, Cesare ; Frankel, Arthur E. / 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. In: Blood. 2005 ; Vol. 106, No. 7. pp. 2527-2529.
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AU - Biffoni, Mauro

AU - Diverio, Daniela

AU - Lo-Coco, Francesco

AU - Foà, Robin

AU - Peschle, Cesare

AU - Frankel, Arthur E.

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