Pediatric acute myelogenous leukemia cells express IL-6 receptors and are sensitive to a recombinant IL6-Pseudomonas exotoxin

K. B. Boayue, L. Gu, A. M. Yeager, R. J. Kreitman, H. W. Findley

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

We have studied IL-6 receptor (IL-6R) expression on AML cells from 15 pediatric patients by immunocytochemistry/flow cytometry, reverse-transcription polymerase chain reaction, and Scatchard analysis. High-affinity IL-6R were detected on leukemic cells from 12 (80%) patients. Binding sites per cell ranged from 140 to 3580 (median 920; mean 1240), with dissociation constants of 0.26 to 0.71 nM. We therefore assessed the in vitro sensitivity of IL-6R+ AML cells to treatment with a recombinant IL6-Pseudomonas exotoxin fusion protein (IL6-PE(4E)), using the XTT cytotoxicity assay. Leukemic cells from eight patients had ID50 values (concentration of IL6-PE(4E) producing a 50% decrease in cell viability) of < 1000 ng/ml (median, 87 ng/ml; mean, 262 ng/ml). Sensitivity to IL6-PE(4E) correlated significantly with receptor number. Normal bone marrow mononuclear cells had undetectable IL6-R expression (< 20 receptors/cell) and were relatively resistant to IL6-PE(4E). To test the efficacy of IL6-PE(4E) for ex vivo purging in an autologous stem cell transplantation setting, we incubated primary IL-6R+ AML cells with 103 ng/ml IL6-PE(4E) for 24 h, followed by inoculation into SCID mice. Mice receiving treated cells showed no leukemic engraftment, while all mice receiving untreated or control-treated cells developed leukemia with a median presymptomatic interval of 55 days. In recipients of IL6-PE(4E) treated cells, no evidence of occult leukemia was detected by PCR analysis of blood and bone marrow cells at 185 days postinoculation. These data suggest that IL-6R are expressed on leukemic cells from a substantial percentage of pediatric AML patients. Furthermore, leukemic cells expressing high numbers of IL6-R may be sensitive to IL6-PE(4E) in an ex vivo purging protocol.

Original languageEnglish (US)
Pages (from-to)182-191
Number of pages10
JournalLeukemia
Volume12
Issue number2
DOIs
StatePublished - 1998

Keywords

  • AML
  • IL6-Pseudomonas exotoxin
  • Interleukin-6 receptor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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