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Modulation of leukotriene signaling inhibiting cell growth in chronic myeloid leukemia
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2016 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, no 8, 1-11 p.Article in journal (Refereed) Epub ahead of print
Abstract [en]

Although tyrosine kinase inhibitors (TKIs) have dramatically improved clinical outcome in chronic myeloid leukemia (CML), cure rarely occurs. This may be due to BCR-ABL-independent, aberrant signaling pathways, one of which leads to leukotriene (LT) formation. Well-recognized as inflammatory mediators, LT can also affect oncogenic mechanisms of several tumors. We have previously discovered elevated LT-synthesis and up-regulated cysteinyl-LT-inducing enzyme in CML. Here we report on dose-dependent inhibition of CML cell growth exerted by specific blockers of LT-signaling. Thus, the cysteinyl-LT1-receptor-antagonist montelukast significantly reduced the growth of K562, KCL22, and KU812 cells, as well as primary CD34(+) blood cells from two CML patients. Adding montelukast to the TKI imatinib caused combined inhibition. No effect was seen on normal bone marrow cells. Similarly, growth inhibition was also observed with the 5-lipoxygenase (LO)-inhibitor BWA4C, the 5-LO-activating-protein-(FLAP)-inhibitor licofelone and the LTB4(BLT1)-receptor-antagonist LY293111. Thus, blocking of aberrant LT-signaling may provide an additional, novel therapeutic possibility in CML.

Place, publisher, year, edition, pages
2016. no 8, 1-11 p.
Keyword [en]
Chronic myeloid leukemia, leukotrienes, pharmacotherapeutics
National Category
Hematology
Identifiers
URN: urn:nbn:se:umu:diva-131376DOI: 10.1080/10428194.2016.1262029PubMedID: 27931141OAI: oai:DiVA.org:umu-131376DiVA: diva2:1073805
Available from: 2017-02-13 Created: 2017-02-13 Last updated: 2017-03-15

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CiteExportLink to record
Permanent link

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Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf