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dc.contributor.authorLucas, Claire*
dc.contributor.authorHarris, Robert*
dc.contributor.authorMcDonald, Elizabeth*
dc.contributor.authorGiannoudis, Athina*
dc.contributor.authorClark, Richard*
dc.date.accessioned2019-04-23T16:03:10Z
dc.date.available2019-04-23T16:03:10Z
dc.date.issued2014-11-01
dc.identifier.citationLucas, C., Harris, R., Giannoudis, A., McDonald, E., & Clark, R. (2014). Low leukotriene B4 receptor 1 leads to ALOX5 downregulation at diagnosis of chronic myeloid leukemia. Haematologica, 99(11), 1710-1715.
dc.identifier.issn0390-6078
dc.identifier.doi10.3324/haematol.2013.101972
dc.identifier.urihttp://hdl.handle.net/10034/622170
dc.description.abstractALOX5 is implicated in chronic myeloid leukemia development in mouse leukemic stem cells, but its importance in human chronic myeloid leukemia is unknown. Functional ALOX5 was assessed using an LTB4 ELISA and ALOX5, and LTB4R1 mRNA expression was determined via a TaqMan gene expression assay. LTB4R1 and 5-LOX protein levels were assessed by cell surface flow cytometry analysis. At diagnosis ALOX5 was below normal in both blood and CD34(+) stem cells in all patients. On treatment initiation, ALOX5 levels increased in all patients except those who were destined to progress subsequently to blast crisis. LTB4 levels were increased despite low ALOX5 expression, suggesting that the arachidonic acid pathway is functioning normally up to the point of LTB4 production. However, the LTB4 receptor (BLT1) protein in newly diagnosed patients was significantly lower than after a period of treatment (P<0.0001). The low level of LTB4R1 at diagnosis explains the downregulation of ALOX5. In the absence of LTB4R1, the arachidonic acid pathway intermediates (5-HEPTE and LTA4) negatively regulate ALOX5. ALOX5 regulation is aberrant in chronic myeloid leukemia patients and may not be important for the development of the disease. Our data suggest caution when extrapolating mouse model data into human chronic myeloid leukemia.
dc.language.isoenen
dc.publisherFerrata Storti Foundationen_US
dc.relation.urlhttp://www.haematologica.org/content/99/11/1710en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectCMLen_US
dc.subjectALOX5en_US
dc.subjectLTB4en_US
dc.titleLow leukotriene B4 receptor 1 leads to ALOX5 downregulation at diagnosis of chronic myeloid leukemiaen_US
dc.typeArticleen_US
dc.identifier.eissn1592-8721
dc.contributor.departmentUniversity of Liverpool, Royal Liverpool University hospital,
dc.identifier.journalHaematologicaen_US
dc.date.accepted2014-08-27
or.grant.openaccessYesen_US
rioxxterms.funderNAen_US
rioxxterms.identifier.projectNAen_US
rioxxterms.versionAMen_US
rioxxterms.licenseref.startdate2014-11
refterms.dateFCD2019-04-18T07:38:14Z
refterms.versionFCDAM
refterms.dateFOA2019-04-23T16:03:11Z


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