{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T05:32:34Z","timestamp":1784352754576,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T00:00:00Z","timestamp":1447372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Myeloma cells thrive in an environment of sustained inflammation, which impacts the development and evolution of the disease, as well as drug resistance. We evaluated the impact of genetic polymorphisms in the Toll\u2010like receptor 4 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4) pathway, which have been implicated in different inflammatory responses in the outcomes of patients with symptomatic multiple myeloma (<jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>) who have received contemporary therapies. We found that the presence of single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s) in both the <jats:italic><jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4<\/jats:italic> and toll\/interleukin\u20101 receptor (<jats:styled-content style=\"fixed-case\">TIR<\/jats:styled-content>)\u2010associated protein (<jats:italic><jats:styled-content style=\"fixed-case\">TIRAP<\/jats:styled-content><\/jats:italic>) genes was associated with lower response to primary therapy mainly for patients who received immunomodulatory drugs but not in patients treated with bortezomib\u2010based therapies. Furthermore, <jats:italic><jats:styled-content style=\"fixed-case\">TIRAP<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> was associated with a significantly shorter progression\u2010free survival and overall survival, independently of other prognostic factors, such as age, transplant, International Staging System stage, lactate dehydrogenase and cytogenetics. This is the first study to demonstrate the effect of <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in <jats:italic><jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\/<jats:styled-content style=\"fixed-case\">TIRAP<\/jats:styled-content><\/jats:italic> in <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>. Our data indicate that genetic variability in the immune system may be associated with different responses to antimyeloma therapies and may be a critical component affecting the natural history of the disease, providing the basis for further investigation of the role of these pathways in myeloma.<\/jats:p>","DOI":"10.1111\/bjh.13786","type":"journal-article","created":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T11:42:12Z","timestamp":1447414932000},"page":"44-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i><scp>TLR<\/scp>4\/<scp>TIRAP<\/scp><\/i> polymorphisms are associated with progression and survival of patients with symptomatic myeloma"],"prefix":"10.1111","volume":"172","author":[{"given":"Tina","family":"Bagratuni","sequence":"first","affiliation":[{"name":"Department of Clinical Therapeutics National and Kapodistrian University of Athens Athens 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