High affinity interleukin-3 receptor expression on blasts from patients with acute myelogenous leukemia correlates with cytotoxicity of a diphtheria toxin/IL-3 fusion protein

R. L. Alexander, J. Ramage, G. L. Kucera, M. A. Caligiuri, A. E. Frankel

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Diphtheria fusion proteins are a novel class of agents for the treatment of chemotherapy resistant AML. We prepared DT388IL3 composed of human interleukin-3 (IL3) fused to the catalytic and translocation domain of diphtheria toxin (DT388) and assessed its activity on patient AML blasts. The number and affinity of IL3 receptors in circulating blasts was measured using a radiolabeled IL3 agonist (SC-65461). Ninety-two percent of patients' blasts had both high and low affinity IL3 receptors. DT388IL3 cytotoxicity (>1 log cell kill) was seen in nine of 25 samples (36%). There was a significant correlation between DT388IL3 log cell kill and blast high affinity IL3 receptor density (P=0.0044). These results show that specific high affinity IL3 binding is one factor important in the sensitivity of patients' leukemic blasts to DT388IL3.

Original languageEnglish (US)
Pages (from-to)875-881
Number of pages7
JournalLeukemia Research
Volume25
Issue number10
DOIs
StatePublished - 2001

Fingerprint

Interleukin-3 Receptors
Diphtheria Toxin
Interleukin-3
Acute Myeloid Leukemia
Proteins
Diphtheria
Catalytic Domain
Drug Therapy
Therapeutics

Keywords

  • Cytokines
  • Diphtheria toxin
  • Fusion protein
  • IL3, Interleukin-3
  • Interleukin-3
  • Neoplasia

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

High affinity interleukin-3 receptor expression on blasts from patients with acute myelogenous leukemia correlates with cytotoxicity of a diphtheria toxin/IL-3 fusion protein. / Alexander, R. L.; Ramage, J.; Kucera, G. L.; Caligiuri, M. A.; Frankel, A. E.

In: Leukemia Research, Vol. 25, No. 10, 2001, p. 875-881.

Research output: Contribution to journalArticle

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AU - Kucera, G. L.

AU - Caligiuri, M. A.

AU - Frankel, A. E.

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AB - Diphtheria fusion proteins are a novel class of agents for the treatment of chemotherapy resistant AML. We prepared DT388IL3 composed of human interleukin-3 (IL3) fused to the catalytic and translocation domain of diphtheria toxin (DT388) and assessed its activity on patient AML blasts. The number and affinity of IL3 receptors in circulating blasts was measured using a radiolabeled IL3 agonist (SC-65461). Ninety-two percent of patients' blasts had both high and low affinity IL3 receptors. DT388IL3 cytotoxicity (>1 log cell kill) was seen in nine of 25 samples (36%). There was a significant correlation between DT388IL3 log cell kill and blast high affinity IL3 receptor density (P=0.0044). These results show that specific high affinity IL3 binding is one factor important in the sensitivity of patients' leukemic blasts to DT388IL3.

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