Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied whether the histamine H2 receptor antagonist, cimetidine, potentiates antiproliferative effects of recombinant alpha interferon (IFN alpha) on in vitro clonal growth of certain normal and malignant hematopoietic cells. Cimetidine alone, at therapeutic serum concentrations, was not inhibitory to the cells studied. IFN alpha alone inhibited the growth of HL-60 leukemic cells only at concentrations greater than 1000 U/ml, whereas with cimetidine, inhibition was seen at greater than 1 U/ml of IFN alpha. The enhancing effect of cimetidine on IFN alpha inhibition of clonal growth was neutralized by histamine and was not seen with histamine H1 receptor antagonist. In HL-60 cells, cimetidine also increased the enzymatic activity of (2'-5')-oligoadenylate synthetase, induced by IFN alpha. The combination of cimetidine and IFN alpha had a synergistic inhibitory effect on the growth of leukemic granulocyte-macrophage colony-forming units (CFU-GM) from chronic myeloid leukemia patients, normal CFU-GM, and normal erythroid burst-forming unit (BFU-E) progenitors. These data suggest that cimetidine may play a role in overcoming resistance to IFN alpha therapy in leukemia, but may also increase IFN alpha hematopoietic toxicity.
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PMID:Effect of alpha interferon on growth of leukemic and normal hematopoietic progenitors. Synergism with H2 histamine receptor antagonists. 271 24