000179089 001__ 179089
000179089 005__ 20240229145532.0
000179089 0247_ $$2doi$$a10.3390/cells11050854
000179089 0247_ $$2pmid$$apmid:35269477
000179089 0247_ $$2pmc$$apmc:PMC8909053
000179089 0247_ $$2altmetric$$aaltmetric:123940032
000179089 037__ $$aDKFZ-2022-00454
000179089 041__ $$aEnglish
000179089 082__ $$a570
000179089 1001_ $$aSidorova, Olga Alexandra$$b0
000179089 245__ $$aRNAi-Mediated Screen of Primary AML Cells Nominates MDM4 as a Therapeutic Target in NK-AML with DNMT3A Mutations.
000179089 260__ $$aBasel$$bMDPI$$c2022
000179089 3367_ $$2DRIVER$$aarticle
000179089 3367_ $$2DataCite$$aOutput Types/Journal article
000179089 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1647250309_16421
000179089 3367_ $$2BibTeX$$aARTICLE
000179089 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000179089 3367_ $$00$$2EndNote$$aJournal Article
000179089 520__ $$aDNA-methyltransferase 3A (DNMT3A) mutations belong to the most frequent genetic aberrations found in adult acute myeloid leukemia (AML). Recent evidence suggests that these mutations arise early in leukemogenesis, marking leukemic progenitors and stem cells, and persist through consolidation chemotherapy, providing a pool for AML relapse. Currently, there are no therapeutic approaches directed specifically against this cell population. To unravel therapeutically actionable targets in mutant DNMT3A-driven AML cells, we have performed a focused RNAi screen in a panel of 30 primary AML samples, all carrying a DNMT3A R882 mutation. As one of the strongest hits, we identified MDM4 as a gene essential for proliferation of primary DNMT3AWT/R882X AML cells. We analyzed a publicly available RNA-Seq dataset of primary normal karyotype (NK) AML samples and found a trend towards MDM4 transcript overexpression particularly in DNMT3A-mutant samples. Moreover, we found that the MDM2/4 inhibitor ALRN-6924 impairs growth of DNMT3AWT/R882X primary cells in vitro by inducing cell cycle arrest through upregulation of p53 target genes. Our results suggest that MDM4 inhibition is a potential target in NK-AML patients bearing DNMT3A R882X mutations.
000179089 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0
000179089 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000179089 650_7 $$2Other$$aDNMT3A
000179089 650_7 $$2Other$$aMDM4
000179089 650_7 $$2Other$$aRNAi
000179089 650_7 $$2Other$$aacute myeloid leukemia
000179089 650_7 $$2Other$$afunctional screen
000179089 7001_ $$aSayed, Shady$$b1
000179089 7001_ $$00000-0002-8245-6006$$aPaszkowski-Rogacz, Maciej$$b2
000179089 7001_ $$00000-0002-2844-053X$$aSeifert, Michael$$b3
000179089 7001_ $$0P:(DE-He78)dd60ad1c45db7fcacc5be5238ad17e7d$$aCamgöz, Aylin$$b4$$udkfz
000179089 7001_ $$00000-0002-6741-0608$$aRoeder, Ingo$$b5
000179089 7001_ $$0P:(DE-He78)2a9091646ed378ef030a77fd32aedf79$$aBornhäuser, Martin$$b6$$udkfz
000179089 7001_ $$00000-0003-1241-2048$$aThiede, Christian$$b7
000179089 7001_ $$00000-0002-4577-3344$$aBuchholz, Frank$$b8
000179089 773__ $$0PERI:(DE-600)2661518-6$$a10.3390/cells11050854$$gVol. 11, no. 5, p. 854 -$$n5$$p854$$tCells$$v11$$x2073-4409$$y2022
000179089 909CO $$ooai:inrepo02.dkfz.de:179089$$pVDB
000179089 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)dd60ad1c45db7fcacc5be5238ad17e7d$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000179089 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)2a9091646ed378ef030a77fd32aedf79$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000179089 9101_ $$0I:(DE-588b)2036810-0$$60000-0003-1241-2048$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000179089 9101_ $$0I:(DE-588b)2036810-0$$60000-0002-4577-3344$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000179089 9131_ $$0G:(DE-HGF)POF4-312$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunktionelle und strukturelle Genomforschung$$x0
000179089 9141_ $$y2022
000179089 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ$$d2021-05-04
000179089 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-05-04
000179089 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-05-04
000179089 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-05-04
000179089 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2021-05-04
000179089 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2021-05-04
000179089 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCELLS-BASEL : 2021$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2022-01-07T08:42:17Z
000179089 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2022-01-07T08:42:17Z
000179089 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review$$d2022-01-07T08:42:17Z
000179089 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-30
000179089 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCELLS-BASEL : 2021$$d2022-11-30
000179089 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lB062 Pädiatrische Neuroonkologie$$x0
000179089 9201_ $$0I:(DE-He78)DD01-20160331$$kDD01$$lDKTK DD zentral$$x1
000179089 980__ $$ajournal
000179089 980__ $$aVDB
000179089 980__ $$aI:(DE-He78)B062-20160331
000179089 980__ $$aI:(DE-He78)DD01-20160331
000179089 980__ $$aUNRESTRICTED