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SYMPATHY

Systems medicine approach to establish individualized treatment of lymphoma and leukemia

We aim to establish a systems medicine program that integrates systematic functional assays, multi-omic profiling, bioinformatic analysis, mathematical modeling and setup towards a clinical exploitation. The basis of the program is a platform to map patient specific pathway activity and drug sensitivity of their primary tumor cells ex- vivo. Signals provided by the microenvironment modify pathway activities, including those targeted by drugs, and thereby can mediate resistance or sensitivity to these drugs. We generate a systems-level understanding of how the microenvironment and the individual genetic and molecular make-up of a tumor interact and modify drug response using a high throughput automated microscopy platform mimicking microenvironment conditions. By comparing drug responses across patients with detailed molecular characterization and the clinical parameters, we obtain a rich set of associations of drug sensitivity with biology, biomarkers and outcome. The long-term aim of this work is to bring biology-based individualized treatment of lymphoma and leukemia into clinical practice.

Publications

Bruch, P.-M., H. A. Giles, C. Kolb, S. A. Herbst, T. Becirovic, T. Roider, J. Lu, S. Scheinost, L. Wagner, J. Huellein, I. Berest, M. Kriegsmann, K. Kriegsmann, C. Zgorzelski, P. Dreger, J. B. Zaugg, C. Müller-Tidow, T. Zenz, W. Huber, and S. Dietrich (2022). "Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL." Mol Syst Biol 18(8): e10855. SYMPATHY  doi.org/10.15252/msb.202110855.

Dietrich, S., M. Oleś, J. Lu, L. Sellner, S. Anders, B. Velten, B. Wu, J. Hüllein, M. da Silva Liberio, T. Walther, L. Wagner, S. Rabe, S. Ghidelli-Disse, M. Bantscheff, A. K. Oleś, M. Słabicki, A. Mock, C. C. Oakes, S. Wang, S. Oppermann, M. Lukas, V. Kim, M. Sill, A. Benner, A. Jauch, L. A. Sutton, E. Young, R. Rosenquist, X. Liu, A. Jethwa, K. S. Lee, J. Lewis, K. Putzker, C. Lutz, D. Rossi, A. Mokhir, T. Oellerich, K. Zirlik, M. Herling, F. Nguyen-Khac, C. Plass, E. Andersson, S. Mustjoki, C. von Kalle, A. D. Ho, M. Hensel, J. Dürig, I. Ringshausen, M. Zapatka, W. Huber, and T. Zenz (2018). "Drug-perturbation-based stratification of blood cancer." The Journal of Clinical Investigation 128(1): 427-445. SYMPATHY  doi.org/10.1172/JCI93801.

Herbst, S. A., V. Kim, T. Roider, E. C. Schitter, P.-M. Bruch, N. Liebers, C. Kolb, M. Knoll, J. Lu, P. Dreger, C. Müller-Tidow, T. Zenz, W. Huber, and S. Dietrich (2023). "Comparing the value of mono- vs coculture for high-throughput compound screening in hematological malignancies." Blood Advances 7(19): 5925-5936. SYMPATHY  doi.org/10.1182/bloodadvances.2022009652.

Herbst, S. A., M. Stolarczyk, T. Becirovic, F. Czernilofsky, Y. Liu, C. Kolb, M. Knoll, M. Herling, C. Muller-Tidow, and S. Dietrich (2021). "Phagocytosis by stroma confounds coculture studies." iScience 24(9): 103062. SYMPATHY  www.ncbi.nlm.nih.gov/pubmed/34585113.

Herbst, S. A., M. Vesterlund, A. J. Helmboldt, R. Jafari, I. Siavelis, M. Stahl, E. C. Schitter, N. Liebers, B. J. Brinkmann, F. Czernilofsky, T. Roider, P.-M. Bruch, M. Iskar, A. Kittai, Y. Huang, J. Lu, S. Richter, G. Mermelekas, H. M. Umer, M. Knoll, C. Kolb, A. Lenze, X. Cao, C. Österholm, L. Wahnschaffe, C. Herling, S. Scheinost, M. Ganzinger, L. Mansouri, K. Kriegsmann, M. Kriegsmann, S. Anders, M. Zapatka, G. Del Poeta, A. Zucchetto, R. Bomben, V. Gattei, P. Dreger, J. Woyach, M. Herling, C. Müller-Tidow, R. Rosenquist, S. Stilgenbauer, T. Zenz, W. Huber, E. Tausch, J. Lehtiö, and S. Dietrich (2022). "Proteogenomics refines the molecular classification of chronic lymphocytic leukemia." Nat Commun 13(6226): 1–18. SYMPATHY  doi.org/10.1038/s41467-022-33385-8.

Janssen, M., C. Schmidt, P.-M. Bruch, M. F. Blank, C. Rohde, A. Waclawiczek, D. Heid, S. Renders, S. Göllner, L. Vierbaum, B. Besenbeck, S. A. Herbst, M. Knoll, C. Kolb, A. Przybylla, K. Weidenauer, A. K. Ludwig, M. Fabre, M. Gu, R. F. Schlenk, F. Stölzel, M. Bornhäuser, C. Röllig, U. Platzbecker, C. Baldus, H. Serve, T. Sauer, S. Raffel, C. Pabst, G. Vassiliou, B. Vick, I. Jeremias, A. Trumpp, J. Krijgsveld, C. Müller-Tidow, and S. Dietrich (2022). "Venetoclax synergizes with gilteritinib in FLT3 wild-type high-risk acute myeloid leukemia by suppressing MCL-1." Blood 140(24): 2594–2610. SYMPATHY  doi.org/10.1182/blood.2021014241.

Liebers, N., P.-M. Bruch, T. Terzer, M. Hernandez-Hernandez, N. Paramasivam, D. Fitzgerald, H. Altmann, T. Roider, C. Kolb, M. Knoll, A. Lenze, U. Platzbecker, C. Röllig, C. Baldus, H. Serve, M. Bornhäuser, D. Hübschmann, C. Müller-Tidow, F. Stölzel, W. Huber, A. Benner, T. Zenz, J. Lu, and S. Dietrich (2023). "Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial." Nature Cancer. SYMPATHY  doi.org/10.1038/s43018-023-00645-5.

Liebers, N., J. Duell, D. Fitzgerald, A. Kerkhoff, D. Noerenberg, E. Kaebisch, F. Acker, S. Fuhrmann, C. Leng, M. Welslau, J. Chemnitz, J. M. Middeke, T. Weber, U. Holtick, R. Trappe, R. Pfannes, R. Liersch, C. Spoer, S. Fuxius, N. Gebauer, L. Caille, T. Geer, C. Koenecke, U. Keller, R. Claus, D. Mougiakakos, S. Mayer, A. Huettmann, C. Pott, A. Trummer, G. Wulf, U. Brunnberg, L. Bullinger, G. Hess, C. Mueller-Tidow, B. Glass, G. Lenz, P. Dreger, and S. Dietrich (2021). "Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas." Blood Adv 5(13): 2707-2716. SYMPATHY  www.ncbi.nlm.nih.gov/pubmed/34196677.

Liebers, N., T. Roider, J. P. Bohn, I. Haberbosch, A. Pircher, B. Ferstl, M. Ebnother, C. M. Wendtner, C. Dearden, G. A. Follows, A. D. Ho, C. Muller-Tidow, P. Dreger, X. Troussard, T. Zenz, and S. Dietrich (2019). "BRAF inhibitor treatment in classic hairy cell leukemia: a long-term follow-up study of patients treated outside clinical trials." Leukemia. SYMPATHY  doi.org/10.1038/s41375-019-0646-y.

Liebers, N., S. O. Schonland, C. Speer, D. Edelmann, P. Schnitzler, H. G. Krausslich, C. Mueller-Tidow, U. Hegenbart, and S. Dietrich (2022). "Seroconversion Rates After the Second COVID-19 Vaccination in Patients With Systemic Light Chain (AL) amyloidosis." Hemasphere 6(3): e688. SYMPATHY  www.ncbi.nlm.nih.gov/pubmed/35187406.

Liebers, N., C. Speer, L. Benning, P.-M. Bruch, I. Kraemer, J. Meissner, P. Schnitzler, H.-G. Kräusslich, P. Dreger, C. Mueller-Tidow, I. Poschke, and S. Dietrich (2022). "Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients." Blood 139(1): 142–147. SYMPATHY  doi.org/10.1182/blood.2021013445.

Roessner, P. M., L. Llaó Cid, E. Lupar, T. Roider, M. Bordas, C. Schifflers, L. Arseni, A.-C. Gaupel, F. Kilpert, M. Krötschel, S. J. Arnold, L. Sellner, D. Colomer, S. Stilgenbauer, S. Dietrich, P. Lichter, A. Izcue, and M. Seiffert (2021). "EOMES and IL-10 regulate antitumor activity of T regulatory type 1 CD4+ T cells in chronic lymphocytic leukemia." Leukemia 35(8): 2311-2324. SYMPATHY  doi.org/10.1038/s41375-021-01136-1.

Roider, T., B. J. Brinkmann, and S. Dietrich (2021). "Processing human lymph node samples for single-cell assays." STAR Protocols. SYMPATHY  doi.org/10.1016/j.xpro.2021.100914.

Roider, T., B. J. Brinkmann, V. Kim, M. Knoll, C. Kolb, P. M. Roessner, M. Bordas, P. Dreger, C. Muller-Tidow, W. Huber, M. Seiffert, and S. Dietrich (2021). "An autologous culture model of nodal B-cell lymphoma identifies ex vivo determinants of response to bispecific antibodies." Blood Adv 5(23): 5060-5071. SYMPATHY  www.ncbi.nlm.nih.gov/pubmed/34587238.

Roider, T., J. Seufert, A. Uvarovskii, F. Frauhammer, M. Bordas, N. Abedpour, M. Stolarczyk, J.-P. Mallm, S. A. Herbst, P.-M. Bruch, H. Balke-Want, M. Hundemer, K. Rippe, B. Goeppert, M. Seiffert, B. Brors, G. Mechtersheimer, T. Zenz, M. Peifer, B. Chapuy, M. Schlesner, C. Müller-Tidow, S. Fröhling, W. Huber, S. Anders, and S. Dietrich (2020). "Dissecting intratumour heterogeneity of nodal B-cell lymphomas at the transcriptional, genetic and drug-response levels." Nat Cell Biol: 1–11. SYMPATHY  doi.org/10.1038/s41556-020-0532-x.