Publications
Wierzbinska JA, Toth R, Ishaque N, Rippe K, Mallm JP, Klett LC, Mertens D, Zenz T, Hielscher T, Seifert M, Küppers R, Assenov Y, Lutsik P, Stilgenbauer S, Roessner PM, Seiffert M, Byrd J, Oakes CC, Plass C, Lipka DB (2020) Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL. Genome Med 12, 29. doi: 10.1186/s13073-020-00724-7
Roessner PM, Hanna BS, Öztürk S, Schulz R, Llaó Cid L, Yazdanparast H, Scheffold A, Colomer D, Stilgenbauer S, Lichter P, Seiffert M. TBET-expressing Th1 CD4+ T-cells accumulate in chronic lymphocytic leukemia but their loss does not impact on disease progression in Eµ-TCL1 mice (2020). Br J Haematol 189, 133-145. doi: 10.1111/bjh.16316
Edelmann J, Holzmann K, Tausch E, Saunderson EA, Jebaraj BMC, Steinbrecher D, Dolnik A, Blatte TJ, Landau DA, Saub J , Estenfelder S, Ibach, Cymbalista F, Leblond V, Delmer A, Bahlo J, Robrecht S, Fischer K, Goede V, Bullinger L, Wu CJ, Mertens D, Ficz G, Gribben JG, Hallek M, Dohner H, Stilgenbauer S (2020) Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1 regulated transcription. Haematologica 105, 1379-1390. doi: 10.3324/haematol.2019.217307
Close V, Close W, Kugler SJ, Reichenzeller M, Yosifov DY, Bloehdorn J, Pan L, Tausch E, Westhoff MA, Dohner H, Stilgenbauer S, Oswald F, Mertens D (2019) FBXW7 mutations reduce binding of NOTCH1, leading to cleaved NOTCH1 accumulation and target gene activation in CLL. Blood 133, 830-839 doi: 10.1182/blood-2018-09-874529
Yosifov DY, Wolf C, Stilgenbauer S, Mertens D. (2019) From Biology to Therapy: The CLL Success Story. Hemasphere 3, e175. doi: 10.1097/HS9.0000000000000175
Jebaraj BMC, Tausch E, Landau DA, Bahlo J, Robrecht S, Taylor-Weiner AN, Bloehdorn J, Scheffold A, Mertens D, Bottcher S, Kneba M, Jager U, Zenz T, Wenger MK, Fingerle-Rowson G, Wendtner C, Fink AM, Wu CJ, Eichhorst, B, Fischer K, Hallek M, Dohner H, Stilgenbauer S (2019) Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia. Leukemia 33(9): 2183-2194 doi:10.1038/s41375-019-0446-4
Tausch E, Close W, Dolnik A, Bloehdorn J, Chyla B, Bullinger L, Dohner H, Mertens D, Stilgenbauer S (2019) Venetoclax resistance and acquired BCL2 mutations in chronic lymphocytic leukemia. Haematologica 104, 997-1007. doi:10.3324/haematol.2019.222588
Scheffold A, Jebaraj BMC, Tausch E, Bloehdorn J, Ghia P, Yahiaoui A, Dolnik A, Blatte TJ, Bullinger L, Dheenadayalan RP, Li L, Schneider C, Chen SS, Chiorazzi N, Dietrich S, Seiffer Mt, Tannheimer S, Dohner H, Mertens, Stilgenbauer (2019) IGF1R as druggable target mediating PI3K-delta inhibitor resistance in a murine model of chronic lymphocytic leukemia. Blood 134, 534-547 doi: 10.1182/blood.2018881029
Schulze-Edinghausen L, Dürr C, Öztürk S, Zucknick M, Benner A, Kalter V, Ohl S, Close V, Wuchter P, Stilgenbauer S, Lichter P, Seiffert M. Dissecting the Prognostic Significance and Functional Role of Progranulin in Chronic Lymphocytic Leukemia. Cancers (Basel) 11, 822 doi: 10.3390/cancers11060822
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 (2019) Linking aberrant chromatin features in chronic lymphocytic leukemia to deregulated transcription factor networks. Mol Syst Biol 15, e8339. doi: 10.15252/msb.20188339
Öztürk S*, Roessner PM*, Schulze-Edinghaus L, Yazdanparast H, Kalter V, Lichter P, Hanna BS and Seiffert M (2019). Rejection of adoptively transferred Eµ-TCL1 chronic lymphocytic cells in C57BL/6 substrains or knockout mouse lines.*shared authorship. Leukemia 33, 1514-1539, 2019 doi: 10.1038/s41375-018-0332-5
Hanna BS*, Roessner PM*, Scheffold A*, Jebaraj BMC, Demerdash Y, Öztürk S, Lichter P, Stilgenbauer S and Seiffert M (2019). PI3K∂ inhibition modulates regulatory and effector T-cell differentiation and function in chronic lymphocytic leukemia. .*shared authorship. Leukemia 33, 1427-1438. doi: 10.1038/s41375-018-0318-3
Hanna BS*, Roessner PM*, Yazdanparast H, Colomer D, Campo E, Kugler S, Yosifov D, Stilgenbauer S, Schmidt M, Gabriel R, Lichter P and Seiffert M (2019). Control of chronic lymphocytic leukemia development by clonally-expanded CD8+ T-cells that undergo functional exhaustion in secondary lymphoid tissues. Leukemia 33, 625-637. doi: 10.1038/s41375-018-0250-6
Wolf, C, Garding A, Filarsky K, Bahlo J, Robrecht S, Becker N, Zucknick M, Rouhi A, Weigel A, Claus R, Weichenhan D, Eichhorst B, Fischer K, Hallek M, Kuchenbauer F, Plass C, Dohner H, Stilgenbauer S, Lichter P and Mertens D (2018) NFATC1 activation by DNA hypomethylation in chronic lymphocytic leukemia correlates with clinical staging and can be inhibited by ibrutinib. In J Cancer 142, 322-333 doi:10.1002/ijc.31057
Haderk F, Schulz R, Iskar M, Cid LL, Worst T, Willmund KV, Schulz A, Warnken U, Seiler J, Benner A, Nessling M, Zenz T, Göbel M, Dürig J, Diederichs S, Paggetti J, Moussay E, Stilgenbauer S, Zapatka M, Lichter P & Seiffert M (2017). Tumor-derived exosomes modulate PD-L1 expression in monocytes. Sci Immunol 2(13) doi: 10.1126/sciimmunol.aah5509.
Molitor J, Mallm JP, Rippe K & Erdel F (2017). Retrieving chromatin patterns from deep sequencing data with correlation functions. Biophys J 112(3):473-490 doi: 10.1016/j.bpj.2017.01.001
Filarsky K, Garding A, Becker N, Wolf C, Zucknick M, Claus R, Weichenhan D, Plass C, Döhne, H, Stilgenbauer S, Lichter P & Mertens D (2016). Krüppel-Like Factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling. Haematologica 101:e249-53. doi: 10.3324/haematol.2015.138172
Oakes CC, Seifert M, Assenov Y, Gu L, Przekopowitz M, Ruppert AS, Wang Q, Imbusch CD, Serva A, Koser SD, Brocks D, Lipka DB, Bogatyrova O, Weichenhan D, Brors B, Rassenti L, Kipps TJ, Mertens D, Zapatka M, Lichter P, Dohner H, Kuppers R, Zenz T, Stilgenbauer S, Byrd JC & Plass C (2016). DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia. Nat Genet 48:253-64. doi: 10.1038/ng.3488
Baer C, Oakes CC, Ruppert AS, Claus R, Kim-Wanner SZ, Mertens D, Zenz T, Stilgenbauer S, Byrd JC & Plass C (2015). Epigenetic silencing of miR-708 enhances NF-kB signaling in chronic lymphocytic leukemia. Int J Cancer 137:1352-61. doi: 10.1002/ijc.29491
Muiño JM, Kuruoglu EE & Arndt PF (2014) Evidence of a cancer type-specific distribution for consecutive somatic mutation distances. Comput Biol Chem 53 Pt A:79-83. doi: 10.1016/j.compbiolchem.2014.08.012
Müller-Ott K, Erdel F, Matveeva A, Hahn M, Mallm JP, Marth C, Zhang Q, Kaltofen S, Schotta G, Höfer T & Rippe K (2014). Specificity, propagation and memory of pericentric heterochromatin. Mol Syst Biol 10:746. doi: 10.15252/msb.20145377 A theoretical framework was developed that describes the spatial extension, stability and propagation of histone modification domains via a 'nucleation and looping' mechanism for a prototypic model system of epigenetic silencing.
Bhattacharya N, Caudron-Herger M, Haebe S, Brady N, Diener S, Nothing M, Dohner H, Stilgenbauer S, Rippe K & Mertens D (2014). Loss of cooperativity of secreted CD40L dose-response on CLL cell viability correlates with enhanced activation of NF-kB. Int J Cancer 136:65-73. doi: 10.1002/ijc.28974 To understand the molecular mechanism of the environment-dependent anti-apoptotic signaling circuitry of CLL cells, an approach was introduced to quantify the effect ligands on the survival of in vitro cultured CLL cells. This works includes the establishment of high-resolution and high-throughput microscopy approaches to evaluate chromatin organization/density and the spatial localization of cellular features by immunostaining.
Mertens D & Stilgenbauer S (2014). "Prognostic and predictive factors in patients with chronic lymphocytic leukemia: relevant in the era of novel treatment approaches?" J Clin Oncol 32(9): 869-872. doi: 10.1200/JCO.2013.53.8421
Oakes CC, Claus R, Gu L, Assenov Y, Hüllein J, Zucknick M, Bieg M, Brocks D, Bogatyrova O, Schmidt CR, Rassenti L, Kipps TJ, Mertens D, Lichter P, Döhner H, Stilgenbauer S, Byrd JC, Zenz T & Plass C (2014). Evolution of DNA methylation is linked to genetic aberrations in chronic lymphocytic leukemia. Cancer Discov. 4:348-361. doi: 10.1158/2159-8290.CD-13-0349This paper reveals a coevolution of genetic and epigenetic aberrations, elucidates the selection of novel DNA methylation patterns and epigenetically identifies a novel CLL subgroup.
Verbruggen P, Heinemann T, Manders E, von Boernstaedt G, van Driel R & Höfer T (2014). Robustness of DNA repair through collective rate control. PLoS Comput Biol 10: e1003438. doi: 10.1371/journal.pcbi.1003438
Knudsen PB, Hanna B, Ohl S, Sellner L, Zenz T, Döhner H, Stilgenbauer S, Larsen TO, Lichter P & Seiffert M (2013). Chaetoglobosin A preferentially induces apoptosis in chronic lymphocytic leukemia cells by targeting the cytoskeleton. Leukemia 28:1289-1298. doi: 10.1038/leu.2013.360The study describes the development amd application of an in-vitro system to test novel candidate therapeutic substances in primary CLL cells.
Schulz A, Dürr C, Zenz T, Döhner H, Stilgenbauer S, Lichter P & Seiffert M (2013). Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary cocultures by altering the myeloid microenvironment. Blood 121:2503-2511. doi: 10.1182/blood-2012-08-447664The in-vitro system from the Knudsen et al. study for testing novel candidate therapeutic substances in primary CLL cells was further advanced and applied.
Meier J, Hovestadt V, Zapatka M, Pscherer A, Lichter P & Seiffert M (2013). Genome-wide identification of translationally inhibited and degraded miR-155 targets using RNA-interacting protein-IP. RNA Biol 10:1017-1029. doi: 10.4161/rna.24553This paper introduces a novel methodology to identify non-coding RNAs important for the pathomechanism of CLL and their targets.
Kugler SJ, Schnaiter A, Stilgenbauer S & Mertens D (2013). Missing the notch in NOTCH1. Leuk Lymphoma 54: 1579-1580. doi: 10.3109/10428194.2013.767459Transcription factors play a special role in the pathomechanism of CLL, and the recurrent mutation of NOTCH1 is expected to impact on epigenetic modifications in CLL cells.
Seifert M, Sellmann L, Bloehdorn J, Wein F, Stilgenbauer S, Dürig J & Küppers R (2012). Cellular origin and pathophysiology of chronic lymphocytic leukemia. J Exp Med 209:2183-2198. doi: 10.1084/jem.20120833The normal counterparts of CLL cells were identified from gene expression profiling and reveal that CLL cells are locked in specific developmental stages.