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, in press.

Haderk, F., Schulz, R., Iskar, M., Cid, L.L., Worst, T., Willmund, K.V., 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. and Seiffert, M. (2017). Tumor-derived exosomes modulate PD-L1 expression in monocytes. Sci Immunol 2(13) doi: 10.1126/sciimmunol.aah5509.

Molitor J., Mallm J.-P., 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., Döhner, H., Stilgenbauer, S., Lichter, P. and 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 C.C., Seifert M., Assenov Y., Gu L., Przekopowitz M., Ruppert A.S., Wang Q., Imbusch C.D., Serva A., Koser S.D., Brocks, D., Lipka, D. B., Bogatyrova, O., Weichenhan, D., Brors, B., Rassenti, L., Kipps, T. J., Mertens, D., Zapatka, M., Lichter, P., Dohner, H., Kuppers, R., Zenz, T., Stilgenbauer, S., Byrd, J. C. & 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, C.C., Ruppert, AS., Claus, R., Kim-Wanner, SZ., Mertens, D., Zenz, T., Stilgenbauer, S., Byrd, J.C. & 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, J. M., Kuruoglu, E. E. and Arndt, P. F. (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, J.-P., 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., and 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. and 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, C. C., Claus, R., Gu, L., Assenov, Y., Hüllein, J., Zucknick, M., Bieg, M., Brocks, D., Bogatyrova, O., Schmidt, C. R., Rassenti, L., Kipps, T. J., Mertens, D., Lichter, P., Döhner, H., Stilgenbauer, S., Byrd, J. C., 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. and Höfer, T. (2014). Robustness of DNA repair through collective rate control. PLoS Comput Biol 10: e1003438. doi: 10.1371/journal.pcbi.1003438

Knudsen, P. B., Hanna, B., Ohl, S., Sellner, L., Zenz, T., Döhner, H., Stilgenbauer, S., Larsen, T. O., Lichter, P. and 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. and 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. and 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, S.J., Schnaiter, A., Stilgenbauer, S. and 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. and 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.


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