000130376 001__ 130376 000130376 005__ 20240228143428.0 000130376 0247_ $$2doi$$a10.1002/ijc.30181 000130376 0247_ $$2pmid$$apmid:27170453 000130376 0247_ $$2ISSN$$a0020-7136 000130376 0247_ $$2ISSN$$a1097-0215 000130376 037__ $$aDKFZ-2017-05455 000130376 041__ $$aeng 000130376 082__ $$a610 000130376 1001_ $$aRadujkovic, Aleksandar$$b0 000130376 245__ $$aExpression of CDKN1C in the bone marrow of patients with myelodysplastic syndrome and secondary acute myeloid leukemia is associated with poor survival after conventional chemotherapy. 000130376 260__ $$aBognor Regis$$bWiley-Liss$$c2016 000130376 3367_ $$2DRIVER$$aarticle 000130376 3367_ $$2DataCite$$aOutput Types/Journal article 000130376 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1522227186_30778 000130376 3367_ $$2BibTeX$$aARTICLE 000130376 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000130376 3367_ $$00$$2EndNote$$aJournal Article 000130376 520__ $$aWe tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34(+) cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin-dependent kinase inhibitor 1C (CDKN1C) and with shorter OS (p < 0.001). In multivariable analysis, higher CDKN1C expression was associated with worse OS (p = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C-positive and -negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54, p = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy (n = 83, 2-year OS 30% versus 58%, p = 0.002). In conclusion, low-proliferative phenotype and CDKN1C expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment-naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy. 000130376 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0 000130376 588__ $$aDataset connected to CrossRef, PubMed, 000130376 650_7 $$2NLM Chemicals$$aAntigens, CD34 000130376 650_7 $$2NLM Chemicals$$aBiomarkers 000130376 650_7 $$2NLM Chemicals$$aCDKN1C protein, human 000130376 650_7 $$2NLM Chemicals$$aCyclin-Dependent Kinase Inhibitor p57 000130376 7001_ $$aDietrich, Sascha$$b1 000130376 7001_ $$aAndrulis, Mindaugas$$b2 000130376 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b3$$udkfz 000130376 7001_ $$aLongerich, Thomas$$b4 000130376 7001_ $$aPellagatti, Andrea$$b5 000130376 7001_ $$aNanda, Kriti$$b6 000130376 7001_ $$aGiese, Thomas$$b7 000130376 7001_ $$aGerming, Ulrich$$b8 000130376 7001_ $$aBaldus, Stefan$$b9 000130376 7001_ $$aBoultwood, Jacqueline$$b10 000130376 7001_ $$aHo, Anthony D$$b11 000130376 7001_ $$aDreger, Peter$$b12 000130376 7001_ $$aLuft, Thomas$$b13 000130376 773__ $$0PERI:(DE-600)1474822-8$$a10.1002/ijc.30181$$gVol. 139, no. 6, p. 1402 - 1413$$n6$$p1402 - 1413$$tInternational journal of cancer$$v139$$x0020-7136$$y2016 000130376 909CO $$ooai:inrepo02.dkfz.de:130376$$pVDB 000130376 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ 000130376 9131_ $$0G:(DE-HGF)POF3-313$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vCancer risk factors and prevention$$x0 000130376 9141_ $$y2016 000130376 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz 000130376 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000130376 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000130376 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000130376 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bINT J CANCER : 2015 000130376 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000130376 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000130376 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000130376 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000130376 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000130376 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000130376 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bINT J CANCER : 2015 000130376 9201_ $$0I:(DE-He78)C060-20160331$$kC060$$lBiostatistik$$x0 000130376 980__ $$ajournal 000130376 980__ $$aVDB 000130376 980__ $$aI:(DE-He78)C060-20160331 000130376 980__ $$aUNRESTRICTED