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To identify factors predicting the duration of progression-free survival (PFS) of MM patients on BTZ treatment, the expression of proteasome and endoplasmic reticulum (ER) stress-related genes was quantified in primary samples from patients receiving a combination of BTZ and dexamethasone (BD). Fifty-six MM patients were stratified into a group with PFS&lt;6 months (<jats:italic>n<\/jats:italic>=33) and a second group with PFS\u2a7e6 months (<jats:italic>n<\/jats:italic>=23). Of the 15 genes analyzed, the expression of activating transcription factor 3 (<jats:italic>ATF3<\/jats:italic>) and <jats:italic>ATF4<\/jats:italic> was significantly lower in patients with shorter PFS (<jats:italic>P<\/jats:italic>=0.0157 and <jats:italic>P<\/jats:italic>=0.0085, respectively). Chromatin immunoprecipitation analysis showed that these ATFs bind each other and transactivate genes encoding the pro-apoptotic transcription factors, <jats:italic>CHOP<\/jats:italic> and <jats:italic>Noxa<\/jats:italic>, which promote ER stress-associated apoptosis. When either ATF3 or ATF4 expression was silenced, MM cells partially lost sensitivity to BTZ treatment. This was accompanied by lower levels of Noxa, CHOP and DR5. Thus low basal expression of <jats:italic>ATF3<\/jats:italic> and <jats:italic>ATF4<\/jats:italic> may attenuate BTZ-induced apoptosis. Hence, ATF3 and ATF4 could potentially be used as biomarkers to predict efficacy of BD therapy in patients with MM.<\/jats:p>","DOI":"10.1038\/bcj.2015.98","type":"journal-article","created":{"date-parts":[[2015,12,4]],"date-time":"2015-12-04T14:21:14Z","timestamp":1449238874000},"page":"e373-e373","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Lower expression of activating transcription factors 3 and 4 correlates with shorter progression-free survival in multiple myeloma patients receiving bortezomib plus dexamethasone therapy"],"prefix":"10.1038","volume":"5","author":[{"given":"T","family":"Narita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Ri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Masaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kusumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Iida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,4]]},"reference":[{"key":"BFbcj201598_CR1","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S1535-6108(04)00120-5","volume":"5","author":"J Adams","year":"2004","unstructured":"Adams J . 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SI received research funding and declares honoraria from Janssen Pharmaceutical K.K. and Celgene Co., Ltd. SI also received research funding from Kyowa Hakko Kirin Co., Ltd, Chugai Pharmaceutical Co., Ltd, Bristol-Myers Squibb, Ono Pharmaceutical Co., Ltd, Nippon Kayaku Co., Ltd, Eli Lilly Japan K.K. and Bayer Yakuhin, Ltd. TI received Research funding from Kyowa Hakko Kirin Co., Ltd., Bayer Pharma AG and Celgene K.K. and received honoraria from Kyowa Hakko Kirin Co., Ltd.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}