000292064 001__ 292064
000292064 005__ 20241015125249.0
000292064 0247_ $$2doi$$a10.1182/bloodadvances.2023011540
000292064 0247_ $$2pmid$$apmid:39093953
000292064 0247_ $$2ISSN$$a2473-9529
000292064 0247_ $$2ISSN$$a2473-9537
000292064 0247_ $$2altmetric$$aaltmetric:166048442
000292064 037__ $$aDKFZ-2024-01572
000292064 041__ $$aEnglish
000292064 082__ $$a610
000292064 1001_ $$00000-0003-2147-3811$$aJankovic, Maja$$b0
000292064 245__ $$aThe E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia.
000292064 260__ $$aWashington, DC$$bAmerican Society of Hematology$$c2024
000292064 3367_ $$2DRIVER$$aarticle
000292064 3367_ $$2DataCite$$aOutput Types/Journal article
000292064 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1728989528_12700
000292064 3367_ $$2BibTeX$$aARTICLE
000292064 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000292064 3367_ $$00$$2EndNote$$aJournal Article
000292064 500__ $$aProteomics and Cancer Cell Signaling Group / 2024 Oct 22;8(20):5315-5329
000292064 520__ $$aFor several decades, induction therapy with nucleoside analogs, in particular cytarabine (Ara-C) and, to a lesser extent, fludarabine, has been the standard of care for patients diagnosed with acute myeloid leukemia (AML). Still, the anti-tumor efficacy of nucleoside analogs is often limited by intrinsic and acquired drug resistance, thereby leading to poor therapeutic response and suboptimal clinical outcomes. Here, we used genome-wide CRISPR-based pharmacogenomic screening to map the genetic factors that modulate the response to nucleoside analogs in AML and identified the E3 ubiquitin ligase Herc1 as a key modulator of Ara-C response in the MLL/AF9 (MA) and the HOXA9/MEIS1 (HM) murine AML models both in vitro and in vivo. Loss of HERC1 enhanced nucleoside analog-induced cell death in both murine and human AML cell lines by compromising cell cycle progression. In-depth proteomic analysis and subsequent validation identified deoxycytidine kinase Dck as a novel target of Herc1 in MA and HM murine cells. We observed that HERC1 is overexpressed in AML compared to other cancer types and higher HERC1 expression is associated with shorter overall survival of patients with AML in the TCGA and BEAT-AML cohorts. Collectively, this study highlights the importance of HERC1 in the response of AML cells to nucleoside analogs, thereby establishing this E3 ubiquitin ligase as a novel predictive biomarker and potential therapeutic target for the treatment of AML.
000292064 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
000292064 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000292064 7001_ $$aPoon, William Wl$$b1
000292064 7001_ $$00000-0002-7256-2649$$aGonzales-Losada, Cristobal$$b2
000292064 7001_ $$aVazquez, Gabriela Galicia$$b3
000292064 7001_ $$aSharif-Askari, Bahram$$b4
000292064 7001_ $$aDing, Yi$$b5
000292064 7001_ $$aCraplet-Desombre, Constance$$b6
000292064 7001_ $$aIlie, Alexandru$$b7
000292064 7001_ $$00000-0002-0039-8800$$aShi, Jiantao$$b8
000292064 7001_ $$00000-0001-7035-5382$$aWang, Yongie$$b9
000292064 7001_ $$0P:(DE-He78)1546aa03aab6491ab3cf01f75ac2b6af$$aJayavelu, Ashok Kumar$$b10$$udkfz
000292064 7001_ $$aOrthwein, Alexandre$$b11
000292064 7001_ $$00000-0001-5324-2167$$aMercier, Francois Emile$$b12
000292064 773__ $$0PERI:(DE-600)2876449-3$$a10.1182/bloodadvances.2023011540$$gp. bloodadvances.2023011540$$n20$$p5315-5329$$tBlood advances$$v8$$x2473-9529$$y2024
000292064 909CO $$ooai:inrepo02.dkfz.de:292064$$pVDB
000292064 9101_ $$0I:(DE-588b)2036810-0$$60000-0001-7035-5382$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000292064 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)1546aa03aab6491ab3cf01f75ac2b6af$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ
000292064 9131_ $$0G:(DE-HGF)POF4-311$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vZellbiologie und Tumorbiologie$$x0
000292064 9141_ $$y2024
000292064 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBLOOD ADV : 2022$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-25
000292064 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bBLOOD ADV : 2022$$d2023-08-25
000292064 9201_ $$0I:(DE-He78)A400-20160331$$kA400$$lKKE Pädiatrische Leukämie$$x0
000292064 980__ $$ajournal
000292064 980__ $$aVDB
000292064 980__ $$aI:(DE-He78)A400-20160331
000292064 980__ $$aUNRESTRICTED