Functional proteogenomic characterization of mantle cell lymphoma
Final Report Abstract
Mantle-cell lymphoma (MCL) is a B-cell Non-Hodgkin-Lymphoma (B-NHL) characterized by molecular and clinical heterogeneity. Despite recent advances in the use of targeted agents, immunochemotherapy, and cell therapeutics, drug resistance and relapses occur frequently. Hence, it is of high relevance to comprehensively characterize MCL, including different layers of biological and disease-related information, to identify high-risk patients and tailor novel therapies based on deep molecular profiles. To this end, we elucidated the proteogenomic landscape of 261 patients with de novo MCL. We used transcriptomic expression data from RNA sequencing and generated global proteome expression data by mass spectrometry analysis from formalin-fixed and paraffin-embedded tissue material. For multi-omics data integration of the different data layers, we applied a multiview latent variable model with domain-informed structured sparsity in the form of B-NHL-related feature sets. By inference of multi-omic latent factors within and across all data modalities, we identified distinct MCL proteogenotypes and multi-omic factors that associate with survival phenotypes. These proteogenotypes were mostly not linked to previously established risk factors, disease characteristics, or morphologic phenotypes. Moreover, characteristic biological motifs were enriched in these proteogenotypes, which were associated with differences in tumor proliferation, immune cell signals, and stromal infiltration. Together, this expands the present biological classification of MCL by including proteogenotypes with prognostic relevance. The integrated proteogenomic dataset provides a comprehensive resource for further molecular and translational research in MCL.
Publications
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High CD34 positive stem cell dosage improves thrombocyte recovery in obese myeloma patients undergoing autologous stem cell transplantation. Leukemia & Lymphoma, 62(13), 3283-3287.
Enßle, Julius C.; Wolf, Sebastian; von Metzler, Ivana; Weber, Sarah; Bialleck, Heike; Seifried, Erhard; Serve, Hubert; Scheich, Sebastian & Steffen, Björn
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64th ASH Annual Meeting 2022 Oral presentation: Portraying Immunity to SARS-COV-2 after mRNA-Vaccination in Patients with Multiple Myeloma
Enssle J.C. et al.
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Enhanced but variant-dependent serological and cellular immune responses to third-dose BNT162b2 vaccination in patients with multiple myeloma. Cancer Cell, 40(6), 587-589.
Enssle, Julius C.; Campe, Julia; Büchel, Sarah; Moter, Alina; See, Frederic; Grießbaum, Katharina; Rieger, Michael A.; Wolf, Sebastian; Ballo, Olivier; Steffen, Björn; Serve, Hubert; Rabenau, Holger F.; Widera, Marek; Bremm, Melanie; Huenecke, Sabine; Ciesek, Sandra; von Metzler, Ivana & Ullrich, Evelyn
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Peripheres Nervensystem. Therapie-Handbuch - Onkologie und Hämatologie, 116-118. Elsevier.
Enßle, Julius C.
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Severe impairment of T-cell responses to BNT162b2 immunization in patients with multiple myeloma. Blood, 139(1), 137-142.
Enßle, Julius C.; Campe, Julia; Schwenger, Amelie; Wiercinska, Eliza; Hellstern, Helen; Dürrwald, Ralf; Rieger, Michael A.; Wolf, Sebastian; Ballo, Olivier; Steffen, Björn; Serve, Hubert; Bonig, Halvard; Rabenau, Holger F.; Widera, Marek; Ciesek, Sandra; Metzler, Ivana von & Ullrich, Evelyn
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The proteogenomic subtypes of acute myeloid leukemia. Cancer Cell, 40(3), 301-317.e12.
Jayavelu, Ashok Kumar; Wolf, Sebastian; Buettner, Florian; Alexe, Gabriela; Häupl, Björn; Comoglio, Federico; Schneider, Constanze; Doebele, Carmen; Fuhrmann, Dominik C.; Wagner, Sebastian; Donato, Elisa; Andresen, Carolin; Wilke, Anne C.; Zindel, Alena; Jahn, Dominique; Splettstoesser, Bianca; Plessmann, Uwe; Münch, Silvia; Abou-El-Ardat, Khali ... & Oellerich, Thomas
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20th CIMT Annual Meeting 2023 Poster presentation: Enssle JC et al., Characterizing immunity after SARS- CoV-2 mRNA-vaccination and infection in patients with Multiple Myeloma
Enssle, Julius C.; Campe, Julia; Moter, Alina; Voit, Isabel; Gessner, Alec; Yu, Ika Weija; Wolf, Sebastian; Steffen, Björn; Oellerich, Thomas; Serve, Hubert; Bremm, Melanie; Huenecke, Sabine; Lohoff, Michael; Vehreschild, Maria; Rabenau, Holger F.; Widera, Marek; Ciesek, Sandra; Rieger, Michael A.; Imkeller, Katharina; Metzler, Ivana von & Ullrich, Evelyn
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65th ASH Annual Meeting 2023 Poster presentation: Immune responses after one versus two Influenza A/B vaccinations in patients with Multiple Myeloma
Julius Enssle, Tonio Brinkschmidt, Ralf Dürrwald, Sebastian Wolf, David Zurmeyer, Björn Steffen, Evelyn Ullrich, Hubert Serve, Thomas Oellerich & Ivana von Metzler
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Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients. Leukemia, 38(1), 168-180.
Enssle, Julius C.; Campe, Julia; Moter, Alina; Voit, Isabel; Gessner, Alec; Yu, Weijia; Wolf, Sebastian; Steffen, Björn; Serve, Hubert; Bremm, Melanie; Huenecke, Sabine; Lohoff, Michael; Vehreschild, Maria; Rabenau, Holger F.; Widera, Marek; Ciesek, Sandra; Oellerich, Thomas; Imkeller, Katharina; Rieger, Michael A. ... & Ullrich, Evelyn
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EHA2023 Congress 2023 Abstract publication: Enssle JC et al., Immune Responses after SARS-CoV-2
mRNA-Vaccination and Infection at Single Cell Resolution in Patients with Multiple Myeloma
Enssle, Julius C.; Campe, Julia; Moter, Alina; Voit, Isabel; Gessner, Alec; Yu, Ika Weija; Wolf, Sebastian; Steffen, Björn; Oellerich, Thomas; Serve, Hubert; Bremm, Melanie; Huenecke, Sabine; Lohoff, Michael; Vehreschild, Maria; Rabenau, Holger F.; Widera, Marek; Ciesek, Sandra; Rieger, Michael A.; Imkeller, Katharina; Metzler, Ivana von & Ullrich, Evelyn
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Impact of BMI on patient outcome in acute myeloid leukaemia patients receiving intensive induction therapy: a real-world registry experience. British Journal of Cancer, 129(7), 1126-1133.
Enßle, Julius C.; Wolf, Sebastian; Scheich, Sebastian; Weber, Sarah; Kramer, Michael; Ruhnke, Leo; Schliemann, Christoph; Mikesch, Jan-Henrik; Krause, Stefan; Sauer, Tim; Hanoun, Maher; Reinhardt, Hans Christian; Kraus, Sabrina; Kaufmann, Martin; Hänel, Mathias; Fransecky, Lars; Burchert, Andreas; Neubauer, Andreas; Crysandt, Martina ... & Steffen, Björn
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Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas. Cancer Discovery, 13(8), 1862-1883.
Scheich, Sebastian; Chen, Jiji; Liu, Jiamin; Schnütgen, Frank; Enssle, Julius C.; Ceribelli, Michele; Thomas, Craig J.; Choi, Jaewoo; Morris, Vivian; Hsiao, Tony; Nguyen, Hang; Wang, Boya; Bolomsky, Arnold; Phelan, James D.; Corcoran, Sean; Urlaub, Henning; Young, Ryan M.; Häupl, Björn; Wright, George W. ... & Staudt, Louis M.
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Treatment with midostaurin and other FLT3 targeting inhibitors is associated with an increased risk of cardiovascular adverse events in patients who underwent allogeneic hematopoietic stem cell transplantation with FLT3-mutated AML. Annals of Hematology, 102(10), 2903-2908.
Cremer, Anjali; Enssle, Julius C.; Pfaff, Saskia; Kouidri, Khouloud; Lang, Fabian; Brandts, Christian; Zeiher, Andreas; Cremer, Sebastian; Steffen, Björn; Serve, Hubert & Bug, Gesine
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Response to Bruton’s tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy. Cancer Cell, 42(2), 238-252.e9.
Phelan, James D.; Scheich, Sebastian; Choi, Jaewoo; Wright, George W.; Häupl, Björn; Young, Ryan M.; Rieke, Sara A.; Pape, Martine; Ji, Yanlong; Urlaub, Henning; Bolomsky, Arnold; Doebele, Carmen; Zindel, Alena; Wotapek, Tanja; Kasbekar, Monica; Collinge, Brett; Huang, Da Wei; Coulibaly, Zana A.; Morris, Vivian M. ... & Oellerich, Thomas
