000130506 001__ 130506 000130506 005__ 20240125162931.0 000130506 0247_ $$2doi$$a10.1002/cncr.24506 000130506 0248_ $$2sideral$$a129738 000130506 037__ $$aART-2009-129738 000130506 041__ $$aeng 000130506 100__ $$aInamdar, Kedar V. 000130506 245__ $$aExpression of eukaryotic initiation factor 4E predicts clinical outcome in patients with mantle cell lymphoma treated with hyper-CVAD and rituximab, alternating with rituximab, high-dose methotrexate, and cytarabine 000130506 260__ $$c2009 000130506 5203_ $$aBACKGROUND:Oncogenic AKT/mammalian target of rapamycin (mTOR) signaling has recently been shownto contribute to tumor survival and proliferation in mantle cell lymphoma (MCL) through its downstreameffector eukaryotic initiation factor 4E (eIF4E), which may control cyclin D1 protein levels. However, the clini-cal significance of eIF4E expression in MCL is unknown.METHODS:The authors investigated the prognosticsignificance of eIF4E expression in 70 MCL patients uniformly treated with hyper-CVAD and rituximab,alternating with the rituximab, high-dose methotrexate, and cytarabine regimen (R-hyper-CVAD). eIF4Eexpression was assessed using tissue biopsy specimens obtained before treatment, immunohistochemicalmethods, and a highly specific monoclonal antibody. Failure-free (FFS) and overall (OS) survival were usedas endpoints in univariate and multivariate survival analysis.RESULTS:High eIF4E expression was found in28 (40%) MCL tumors. After a median follow-up of 51 months for survivors, the 5-year FFS was 20.6% forpatients with high eIF4E expression, compared with 63.5% for patients with low or no eIF4E expression (P¼.01, log-rank). Similarly, the 5-year OS was 40.1% for patients with high eIF4E expression, compared with73.8% for patients with low or no eIF4E expression (P¼.018, log-rank). In multivariate analysis, eIF4E expres-sion was associated with poorer FFS and OS, along with age>60 years and highb2–microglobulin in the finalprognostic model.CONCLUSIONS:In summary, eIF4E, which seems to recapitulate most of the biologiceffects of mTOR signaling in MCL, is an independent predictor of clinical outcome in MCL patients uniformlytreated with the R-hyper-CVAD regimen 000130506 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000130506 590__ $$a5.418$$b2009 000130506 591__ $$aONCOLOGY$$b21 / 164 = 0.128$$c2009$$dQ1$$eT1 000130506 655_4 $$ainfo:eu-repo/semantics/article 000130506 700__ $$aRomaguera, Jorge E. 000130506 700__ $$aDrakos, Elias 000130506 700__ $$aKnoblock, Ronald J. 000130506 700__ $$0(orcid)0000-0003-2078-8205$$aGarcia, Mar 000130506 700__ $$aLeventaki, Vasiliki 000130506 700__ $$aMedeiros, L. Jeffrey 000130506 700__ $$aRassidakis, George Z. 000130506 773__ $$g115, 20 (2009), 4727-4736$$pCancer$$tCANCER$$x0008-543X 000130506 8564_ $$s397227$$uhttps://zaguan.unizar.es/record/130506/files/texto_completo.pdf 000130506 8564_ $$s1998107$$uhttps://zaguan.unizar.es/record/130506/files/texto_completo.jpg?subformat=icon$$xicon 000130506 909CO $$ooai:zaguan.unizar.es:130506$$particulos$$pdriver 000130506 951__ $$a2024-01-25-15:16:19 000130506 980__ $$aARTICLE