Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation

A possible target for therapy with recombinant IL6-Pseudomonas exotoxin

L. Gu, M. Zhou, I. Jurickova, Andrew M Yeager, R. J. Kreitman, C. N. Phillips, H. W. Findley

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have detected expression of interleukin-6 receptors (IL-6R) by primary leukemic cells from three of six patients with t(4;11)+ ALL. Scatchard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on these cells (median, 1560; mean, 1540). All three IL-6R+ cases also expressed CD33, which was not expressed on IL-6R-negative cases. To determine if these receptors could serve as a target for a recombinant ligand-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6-Pseudomonas exotoxin (IL6-PE(4E)) fusion protein, in which the toxicity and specificity of the chimeric toxin was enhanced by substitution of four glutamine residues for naturally occurring amino acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE(4E) in a 48-h cytotoxicity assay, with ID50 values (concentrations causing 50% decrease in viability) ranging from 23 ng/ml to 92 ng/ml (median, 61; mean, 58). Furthermore, incubation of these cells with 103 ng/ml IL6-toxin for 24 h prevented their subsequent engraftment in SCID mice. Thus, IL6-PE(4E) may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease.

Original languageEnglish (US)
Pages (from-to)1779-1786
Number of pages8
JournalLeukemia
Volume11
Issue number10
StatePublished - 1997
Externally publishedYes

Fingerprint

Interleukin-6 Receptors
Exotoxins
Pseudomonas
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Interleukin-6
Pediatrics
Therapeutics
Immunotoxins
SCID Mice
Autologous Transplantation
Glutamine
Bone Marrow Transplantation
Ligands
Amino Acids
Drug Therapy

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation : A possible target for therapy with recombinant IL6-Pseudomonas exotoxin. / Gu, L.; Zhou, M.; Jurickova, I.; Yeager, Andrew M; Kreitman, R. J.; Phillips, C. N.; Findley, H. W.

In: Leukemia, Vol. 11, No. 10, 1997, p. 1779-1786.

Research output: Contribution to journalArticle

@article{f039149401e044f2a899a841ef4d6a99,
title = "Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation: A possible target for therapy with recombinant IL6-Pseudomonas exotoxin",
abstract = "We have detected expression of interleukin-6 receptors (IL-6R) by primary leukemic cells from three of six patients with t(4;11)+ ALL. Scatchard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on these cells (median, 1560; mean, 1540). All three IL-6R+ cases also expressed CD33, which was not expressed on IL-6R-negative cases. To determine if these receptors could serve as a target for a recombinant ligand-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6-Pseudomonas exotoxin (IL6-PE(4E)) fusion protein, in which the toxicity and specificity of the chimeric toxin was enhanced by substitution of four glutamine residues for naturally occurring amino acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE(4E) in a 48-h cytotoxicity assay, with ID50 values (concentrations causing 50{\%} decrease in viability) ranging from 23 ng/ml to 92 ng/ml (median, 61; mean, 58). Furthermore, incubation of these cells with 103 ng/ml IL6-toxin for 24 h prevented their subsequent engraftment in SCID mice. Thus, IL6-PE(4E) may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease.",
keywords = "ALL, IL6-Pseudomonas exotoxin, Interleukin-6 receptor",
author = "L. Gu and M. Zhou and I. Jurickova and Yeager, {Andrew M} and Kreitman, {R. J.} and Phillips, {C. N.} and Findley, {H. W.}",
year = "1997",
language = "English (US)",
volume = "11",
pages = "1779--1786",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation

T2 - A possible target for therapy with recombinant IL6-Pseudomonas exotoxin

AU - Gu, L.

AU - Zhou, M.

AU - Jurickova, I.

AU - Yeager, Andrew M

AU - Kreitman, R. J.

AU - Phillips, C. N.

AU - Findley, H. W.

PY - 1997

Y1 - 1997

N2 - We have detected expression of interleukin-6 receptors (IL-6R) by primary leukemic cells from three of six patients with t(4;11)+ ALL. Scatchard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on these cells (median, 1560; mean, 1540). All three IL-6R+ cases also expressed CD33, which was not expressed on IL-6R-negative cases. To determine if these receptors could serve as a target for a recombinant ligand-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6-Pseudomonas exotoxin (IL6-PE(4E)) fusion protein, in which the toxicity and specificity of the chimeric toxin was enhanced by substitution of four glutamine residues for naturally occurring amino acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE(4E) in a 48-h cytotoxicity assay, with ID50 values (concentrations causing 50% decrease in viability) ranging from 23 ng/ml to 92 ng/ml (median, 61; mean, 58). Furthermore, incubation of these cells with 103 ng/ml IL6-toxin for 24 h prevented their subsequent engraftment in SCID mice. Thus, IL6-PE(4E) may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease.

AB - We have detected expression of interleukin-6 receptors (IL-6R) by primary leukemic cells from three of six patients with t(4;11)+ ALL. Scatchard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on these cells (median, 1560; mean, 1540). All three IL-6R+ cases also expressed CD33, which was not expressed on IL-6R-negative cases. To determine if these receptors could serve as a target for a recombinant ligand-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6-Pseudomonas exotoxin (IL6-PE(4E)) fusion protein, in which the toxicity and specificity of the chimeric toxin was enhanced by substitution of four glutamine residues for naturally occurring amino acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE(4E) in a 48-h cytotoxicity assay, with ID50 values (concentrations causing 50% decrease in viability) ranging from 23 ng/ml to 92 ng/ml (median, 61; mean, 58). Furthermore, incubation of these cells with 103 ng/ml IL6-toxin for 24 h prevented their subsequent engraftment in SCID mice. Thus, IL6-PE(4E) may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease.

KW - ALL

KW - IL6-Pseudomonas exotoxin

KW - Interleukin-6 receptor

UR - http://www.scopus.com/inward/record.url?scp=0030704212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030704212&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 1779

EP - 1786

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 10

ER -