RGD Reference Report - Treatment of acute myelocytic leukemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukemia model. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Treatment of acute myelocytic leukemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukemia model.

Authors: Rozemuller, H  Rombouts, WJ  Touw, IP  FitzGerald, DJ  Kreitman, RJ  Pastan, I  Hagenbeek, A  Martens, AC 
Citation: Rozemuller H, etal., Leukemia. 1996 Nov;10(11):1796-803.
RGD ID: 11062010
Pubmed: PMID:8892684   (View Abstract at PubMed)

We studied the applicability of interleukin-6 Pseudomonas exotoxin fusion protein (IL-6PE4E) for treatment of acute myelocytic leukemia (AML). Leukemic cells from five out of 10 AML patients studied expressed IL-6 receptor (IL-6R) and proliferation in vitro was inhibited in four of these cases. The potential of this approach in vivo was tested in a pre-clinical model for AML; the Brown Norway acute myelocytic leukemia (BNML). To obtain IL-6R expression levels on BNML cells comparable to the numbers expressed on human AML, human IL-6R gene transfectants of the BNML sub-line LT12 (LT12/IL-6R) were generated. IL-6PE4E is cytotoxic in vitro to LT12/IL-6R expressing 1400 high affinity IL-6R per cell with 50% inhibition of DNA synthesis at 1 ng/ml. In vivo treatment of leukemic rats carrying LT12/IL-6R leukemia indicated that the maximal tolerated dose of IL-6PE4E was 275 +/- 25 microg/kg/day, when continuously administered for 7 days and resulted in a 90% reduction in leukemic cell load. At this dose level of IL-6PE4E no reduction of normal hemopoietic progenitors was seen in non-leukemic rats. At higher dose levels (350-1050 microg/kg/day) severe systemic toxicity was encountered. On the basis of these pre-clinical studies the feasibility of growth factor-toxins for selective in vivo targeting to AML cells is evaluated.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL6Humanacute myeloid leukemia treatmentIMP human protein in a rat modelRGD 
Il6Ratacute myeloid leukemia treatmentISOIL6 (Homo sapiens)human protein in a rat modelRGD 
Il6Mouseacute myeloid leukemia treatmentISOIL6 (Homo sapiens)human protein in a rat modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il6  (interleukin 6)

Genes (Mus musculus)
Il6  (interleukin 6)

Genes (Homo sapiens)
IL6  (interleukin 6)


Additional Information