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Bridging Group Mechanisms of Leukemogenesis

PD Dr. Daniel Mertens

Inactivation of 13q14 in leukemic cells. Candidate genes in chromosomal band 13q14 are monoallelically expressed in non-malignant cells due to an epig
© dkfz.de

Cancer patients die from resistance to therapy and metastasis. These processes are based on genetic and epigenetic aberrations and require the support of the tumor microenvironment that supplies pro-survival and protective stimuli. Understanding the molecular mechanism of these processes will allow one to target aberrant (epi)genetic pathways, interrupt the support of the microenvironment and address resistance to therapy. The Cooperation Unit between the DKFZ and the University Hospital of Ulm is ideally suited to translate molecular findings on chronic leukemia towards clinical application with respect to prognostication and therapy.

Overview of projects:

  1. The microenvironment as a therapeutic target in chronic lymphocytic leukemia.
  2. Ubiquitination and NOTCH1 signaling in leukemia.
  3. Epigenetic aberrations explain leukemogenesis and help prognostication of patients.

Contact

PD Dr. Daniel Mertens
Mechanisms of Leukemogenesis (B061)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 731 500 45870

Selected Publications

  • Oxidative stress as candidate therapeutic target to overcome microenvironmental protection of CLL. Yosifov DY, Idler I, Bhattacharya N, Reichenzeller M, Close V, Ezerina D, Scheffold A, Jebaraj BMC, Kugler S, Bloehdorn J, Bahlo J, Robrecht S, Eichhorst B, Fischer K, Weigel A, Busch H, Lichter P, Döhner H, Dick TP, Stilgenbauer S, Mertens D. Leukemia. 2020 Jan;34(1):115-127. doi: 10.1038/s41375-019-0513-x. Epub 2019 Jul 12. PMID: 31300746
  • Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks. Mallm JP, Iskar M, Ishaque N, Klett LC, Kugler SJ, Muino JM, Teif VB, Poos AM, Großmann S, Erdel F, Tavernari D, Koser SD, Schumacher S, Brors B, König R, Remondini D, Vingron M, Stilgenbauer S, Lichter P, Zapatka M, Mertens D*, Rippe K*. Mol Syst Biol. 2019 May 22;15(5):e8339. doi: 10.15252/msb.20188339. PMID: 31118277
  • FBXW7 mutations reduce binding of NOTCH1, leading to cleaved NOTCH1 accumulation and target gene activation in CLL. Close V, Close W, Kugler SJ, Reichenzeller M, Yosifov DY, Bloehdorn J, Pan L, Tausch E, Westhoff MA, Döhner H, Stilgenbauer S, Oswald F*, Mertens D*. Blood. 2019 Feb 21;133(8):830-839. doi: 10.1182/blood-2018-09-874529. Epub 2018 Dec 3. PMID: 30510140
  • Comprehensive microRNA expression profiling in cerebrospinal fluid distinguishes between neurological disease classes. Grasedieck S, Mulaw M, Sperb N, Wessinger K, Rouhi A, Bommer M, Bromberg JEC, Otto M, Tumani H, von Arnim CAF, Mertens D*, Kuchenbauer F*. Neuropathol Appl Neurobiol. 2019 Apr;45(3):318-323. doi: 10.1111/nan.12491. Epub 2018 May 21. PMID: 29679382
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