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Author Christian Wichmann

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Tumor cell lysis and synergistically enhanced antibody-dependent cell-mediated cytotoxicity by NKG2D engagement with a bispecific immunoligand targeting the HER2 antigen.

Christian Kellner, Sebastian Lutz, Hans-Heinrich Oberg, Daniela Wesch, Anna Otte, Katarina J Diemer, Hauke Wilcken, Dirk Bauerschlag, Claus-Christian Glüer, Christian Wichmann, Dieter Kabelitz, Jeanette H W Leusen, Katja Klausz, Andreas Humpe, Martin Gramatzki, Matthias Peipp,

Natural killer group 2 member D (NKG2D) plays an important role in the regulation of natural killer (NK) cell cytotoxicity in cancer immune surveillance. With the aim of redirecting NK cell cytotoxicity against tumors, the NKG2D ligand UL-16 binding protein 2 (ULBP2) was fused to a single-chain fragment variable (scFv) ... Read more >>

Biol Chem (Biological chemistry)
[2021, :]

Cited: 0 times

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Reduction of RUNX1 transcription factor activity by a CBFA2T3-mimicking peptide: application to B cell precursor acute lymphoblastic leukemia.

Hélène Jakobczyk, Lydie Debaize, Benoit Soubise, Stéphane Avner, Jérémie Rouger-Gaudichon, Séverine Commet, Yan Jiang, Aurélien A Sérandour, Anne-Gaëlle Rio, Jason S Carroll, Christian Wichmann, Michael Lie-A-Ling, Georges Lacaud, Laurent Corcos, Gilles Salbert, Marie-Dominique Galibert, Virginie Gandemer, Marie-Bérengère Troadec,

<h4>Background</h4>B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer. Identifying key players involved in proliferation of BCP-ALL cells is crucial to propose new therapeutic targets. Runt Related Transcription Factor 1 (RUNX1) and Core-Binding Factor Runt Domain Alpha Subunit 2 Translocated To 3 (CBFA2T3, ETO2, MTG16) are ... Read more >>

J Hematol Oncol (Journal of hematology & oncology)
[2021, 14(1):47]

Cited: 1 time

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Radiolabelling and preclinical characterization of 89Zr-Df-radiolabelled bispecific anti-PD-L1/TGF-βRII fusion protein bintrafusp alfa.

Ingrid Julienne Georgette Burvenich, Yit Wooi Goh, Nancy Guo, Hui Kong Gan, Angela Rigopoulos, Diana Cao, Zhanqi Liu, Uwe Ackermann, Christian Werner Wichmann, Alexander Franklin McDonald, Nhi Huynh, Graeme Joseph O'Keefe, Sylvia Jie Gong, Fiona Elizabeth Scott, Linghui Li, Wanping Geng, Anup Zutshi, Yan Lan, Andrew Mark Scott,

<h4>Purpose</h4>Τhis study aimed to optimize the <sup>89</sup>Zr-radiolabelling of bintrafusp alfa investigational drug product and controls, and perform the in vitro and in vivo characterization of <sup>89</sup>Zr-Df-bintrafusp alfa and <sup>89</sup>Zr-Df-control radioconjugates.<h4>Methods</h4>Bintrafusp alfa (anti-PD-L1 human IgG1 antibody fused to TGF-β receptor II (TGF-βRII), avelumab (anti-PD-L1 human IgG1 control antibody), isotype control (mutated ... Read more >>

Eur J Nucl Med Mol Imaging (European journal of nuclear medicine and molecular imaging)
[2021, 48(10):3075-3088]

Cited: 0 times

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Automated radiosynthesis of [68 Ga]Ga-PSMA-11 and [177 Lu]Lu-PSMA-617 on the iPHASE MultiSyn module for clinical applications.

Christian W Wichmann, Uwe Ackermann, Stan Poniger, Kenneth Young, Benjamin Nguyen, Gordon Chan, John Sachinidis, Andrew M Scott,

Prostate-specific membrane antigen (PSMA)-targeted imaging and therapy of prostate cancer using theranostic pairs is rapidly changing clinical practice. To facilitate clinical trials, fully automated procedures for the radiosyntheses of [<sup>68</sup> Ga]Ga-PSMA-11 and [<sup>177</sup> Lu]Lu-PSMA-617 were developed from commercially available precursors using the cassette based iPHASE MultiSyn module. Formulated and sterile ... Read more >>

J Labelled Comp Radiopharm (Journal of labelled compounds & radiopharmaceuticals)
[2021, 64(3):140-146]

Cited: 2 times

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ZBTB7A prevents RUNX1-RUNX1T1-dependent clonal expansion of human hematopoietic stem and progenitor cells.

Enric Redondo Monte, Anja Wilding, Georg Leubolt, Paul Kerbs, Johannes W Bagnoli, Luise Hartmann, Wolfgang Hiddemann, Linping Chen-Wichmann, Stefan Krebs, Helmut Blum, Monica Cusan, Binje Vick, Irmela Jeremias, Wolfgang Enard, Sebastian Theurich, Christian Wichmann, Philipp A Greif,

ZBTB7A is frequently mutated in acute myeloid leukemia (AML) with t(8;21) translocation. However, the oncogenic collaboration between mutated ZBTB7A and the RUNX1-RUNX1T1 fusion gene in AML t(8;21) remains unclear. Here, we investigate the role of ZBTB7A and its mutations in the context of normal and malignant hematopoiesis. We demonstrate that ... Read more >>

Oncogene (Oncogene)
[2020, 39(15):3195-3205]

Cited: 4 times

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Synthesis and validation of [18F]mBPET-1, a fluorine-18 labelled mTOR inhibitor derivative based on a benzofuran backbone.

Christian W Wichmann, Yit Wooi Goh, Adam C Parslow, Angela Rigopoulos, Nancy Guo, Andrew M Scott, Uwe Ackermann, Jonathan M White,

BACKGROUND:Targeted therapy of HER2 positive breast cancer has led to clinical success in some cases with primary and secondary resistance being major obstacles. Due to the substantial involvement of mTOR kinase in cell growth and proliferation pathways it is now targeted in combination treatments to counteract HER2 targeted therapy resistance. ... Read more >>

EJNMMI Radiopharm Chem (EJNMMI radiopharmacy and chemistry)
[2020, 5(1):3]

Cited: 1 time

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The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation.

Natalia Martinez-Soria, Lynsey McKenzie, Julia Draper, Anetta Ptasinska, Hasan Issa, Sandeep Potluri, Helen J Blair, Anna Pickin, Asmida Isa, Paulynn Suyin Chin, Ricky Tirtakusuma, Daniel Coleman, Sirintra Nakjang, Salam Assi, Victoria Forster, Mojgan Reza, Ed Law, Philip Berry, Dorothee Mueller, Cameron Osborne, Alex Elder, Simon N Bomken, Deepali Pal, James M Allan, Gareth J Veal, Peter N Cockerill, Christian Wichmann, Josef Vormoor, Georges Lacaud, Constanze Bonifer, Olaf Heidenreich,

Cancer Cell (Cancer cell)
[2019, 35(4):705]

Cited: 3 times

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Oncogenic Deregulation of Cell Adhesion Molecules in Leukemia.

Roland Windisch, Nina Pirschtat, Christian Kellner, Linping Chen-Wichmann, Jörn Lausen, Andreas Humpe, Daniela S Krause, Christian Wichmann,

Numerous cell⁻cell and cell⁻matrix interactions within the bone marrow microenvironment enable the controlled lifelong self-renewal and progeny of hematopoietic stem and progenitor cells (HSPCs). On the cellular level, this highly mutual interaction is granted by cell adhesion molecules (CAMs) integrating differentiation, proliferation, and pro-survival signals from the surrounding microenvironment to ... Read more >>

Cancers (Basel) (Cancers)
[2019, 11(3):]

Cited: 9 times

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The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation.

Natalia Martinez-Soria, Lynsey McKenzie, Julia Draper, Anetta Ptasinska, Hasan Issa, Sandeep Potluri, Helen J Blair, Anna Pickin, Asmida Isa, Paulynn Suyin Chin, Ricky Tirtakusuma, Daniel Coleman, Sirintra Nakjang, Salam Assi, Victoria Forster, Mojgan Reza, Ed Law, Philip Berry, Dorothee Mueller, Cameron Osborne, Alex Elder, Simon N Bomken, Deepali Pal, James M Allan, Gareth J Veal, Gareth J Veal, Peter N Cockerill, Christian Wichmann, Josef Vormoor, Georges Lacaud, Georges Lacaud, Constanze Bonifer, Olaf Heidenreich,

Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets. We used epigenomic profiling data for an RNAi screen to interrogate the transcriptional network maintaining t(8;21) AML. This strategy identified Cyclin D2 (CCND2) as a crucial ... Read more >>

Cancer Cell (Cancer cell)
[2018, 34(4):626-642.e8]

Cited: 30 times

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Changes in the microRNA expression profile during blood storage.

Anna Haberberger, Benedikt Kirchner, Irmgard Riedmaier, Reinhard Henschler, Christian Wichmann, Raymund Buhmann, Michael W Pfaffl,

<h4>Objectives</h4>For several decades, autologous blood doping (ABD) in sports has been a major problem, and even today there is still no reliable method for satisfactorily detecting ABD. For this kind of doping, stored individual erythrocytes are used to increase stamina and endurance caused by a higher erythrocyte level in the ... Read more >>

BMJ Open Sport Exerc Med (BMJ open sport & exercise medicine)
[2018, 4(1):e000354]

Cited: 3 times

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Compatibility of RUNX1/ETO fusion protein modules driving CD34+ human progenitor cell expansion.

Linping Chen-Wichmann, Marina Shvartsman, Caro Preiss, Colin Hockings, Roland Windisch, Enric Redondo Monte, Georg Leubolt, Karsten Spiekermann, Jörn Lausen, Christian Brendel, Manuel Grez, Philipp A Greif, Christian Wichmann,

Chromosomal translocations represent frequent events in leukemia. In t(8;21)+ acute myeloid leukemia, RUNX1 is fused to nearly the entire ETO protein, which contains four conserved nervy homology regions, NHR1-4. Furthermore RUNX1/ETO interacts with ETO-homologous proteins via NHR2, thereby multiplying NHR domain contacts. As shown recently, RUNX1/ETO retains oncogenic activity upon ... Read more >>

Oncogene (Oncogene)
[2019, 38(2):261-272]

Cited: 2 times

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GFI1 is required for RUNX1/ETO positive acute myeloid leukemia.

Anna E Marneth, Lacramioara Botezatu, Judith M Hönes, Jimmy C L Israël, Judith Schütte, Lothar Vassen, Robert F Lams, Saskia M Bergevoet, Laura Groothuis, Amit Mandoli, Joost H A Martens, Gerwin Huls, Joop H Jansen, Ulrich Dührsen, Tobias Berg, Tarik Möröy, Christian Wichmann, Mia-Chia Lo, Dong-Er Zhang, Bert A van der Reijden, Cyrus Khandanpour,

Haematologica (Haematologica)
[2018, 103(9):e395-e399]

Cited: 6 times

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Loss of Wilms tumor 1 protein is a marker for apoptosis in response to replicative stress in leukemic cells.

Miriam Pons, Claudia M Reichardt, Dorle Hennig, Abinaya Nathan, Nicole Kiweler, Carol Stocking, Christian Wichmann, Markus Christmann, Falk Butter, Sigrid Reichardt, Günter Schneider, Thorsten Heinzel, Christoph Englert, Jörg Hartkamp, Oliver H Krämer, Nisintha Mahendrarajah,

A remaining expression of the transcription factor Wilms tumor 1 (WT1) after cytotoxic chemotherapy indicates remaining leukemic clones in patients. We determined the regulation and relevance of WT1 in leukemic cells exposed to replicative stress and DNA damage. To induce these conditions, we used the clinically relevant chemotherapeutics hydroxyurea and ... Read more >>

Arch Toxicol (Archives of toxicology)
[2018, 92(6):2119-2135]

Cited: 5 times

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ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia.

Cécile Thirant, Cathy Ignacimouttou, Cécile K Lopez, M'Boyba Diop, Lou Le Mouël, Clarisse Thiollier, Aurélie Siret, Phillipe Dessen, Zakia Aid, Julie Rivière, Philippe Rameau, Céline Lefebvre, Mehdi Khaled, Guy Leverger, Paola Ballerini, Arnaud Petit, Hana Raslova, Catherine L Carmichael, Benjamin T Kile, Eric Soler, John D Crispino, Christian Wichmann, Françoise Pflumio, Jürg Schwaller, William Vainchenker, Camille Lobry, Nathalie Droin, Olivier A Bernard, Sébastien Malinge, Thomas Mercher,

Chimeric transcription factors are a hallmark of human leukemia, but the molecular mechanisms by which they block differentiation and promote aberrant self-renewal remain unclear. Here, we demonstrate that the ETO2-GLIS2 fusion oncoprotein, which is found in aggressive acute megakaryoblastic leukemia, confers megakaryocytic identity via the GLIS2 moiety while both ETO2 ... Read more >>

Cancer Cell (Cancer cell)
[2017, 31(3):452-465]

Cited: 25 times

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Suppression of RUNX1/ETO oncogenic activity by a small molecule inhibitor of tetramerization.

Julia Schanda, Chun-Wei Lee, Katharina Wohlan, Uta Müller-Kuller, Hana Kunkel, Isabell Quagliano-Lo Coco, Stefan Stein, Alexander Metz, Joachim Koch, Jörn Lausen, Uwe Platzbecker, Hind Medyouf, Holger Gohlke, Michael Heuser, Matthias Eder, Manuel Grez, Michaela Scherr, Christian Wichmann,

Haematologica (Haematologica)
[2017, 102(5):e170-e174]

Cited: 8 times

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Kindlin-2 Modulates the Survival, Differentiation, and Migration of Induced Pluripotent Cell-Derived Mesenchymal Stromal Cells.

Mohsen Moslem, Reto Eggenschwiler, Christian Wichmann, Raymund Buhmann, Tobias Cantz, Reinhard Henschler,

Kindlin-2 is a multidomain intracellular protein that can be recruited to <i>β</i>-integrin domains to activate signaling, initiate transcriptional programs, and bind to E-cadherin. To explore its involvement in cell fate decisions in mesenchymal cells, we studied the effects of Kindlin-2 modification (overexpression/knockdown) in induced pluripotent cell-derived mesenchymal stromal cells (iPSC-MSCs). ... Read more >>

Stem Cells Int (Stem cells international)
[2017, 2017:7316354]

Cited: 3 times

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ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation.

Luise Hartmann, Sayantanee Dutta, Sabrina Opatz, Sebastian Vosberg, Katrin Reiter, Georg Leubolt, Klaus H Metzeler, Tobias Herold, Stefanos A Bamopoulos, Kathrin Bräundl, Evelyn Zellmeier, Bianka Ksienzyk, Nikola P Konstandin, Stephanie Schneider, Karl-Peter Hopfner, Alexander Graf, Stefan Krebs, Helmut Blum, Jan Moritz Middeke, Friedrich Stölzel, Christian Thiede, Stephan Wolf, Stefan K Bohlander, Caroline Preiss, Linping Chen-Wichmann, Christian Wichmann, Maria Cristina Sauerland, Thomas Büchner, Wolfgang E Berdel, Bernhard J Wörmann, Jan Braess, Wolfgang Hiddemann, Karsten Spiekermann, Philipp A Greif,

The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% ... Read more >>

Nat Commun (Nature communications)
[2016, 7:11733]

Cited: 29 times

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MiR144/451 Expression Is Repressed by RUNX1 During Megakaryopoiesis and Disturbed by RUNX1/ETO.

Nicole Kohrs, Stephan Kolodziej, Olga N Kuvardina, Julia Herglotz, Jasmin Yillah, Stefanie Herkt, Alexander Piechatzek, Gabriela Salinas Riester, Thomas Lingner, Christian Wichmann, Halvard Bonig, Erhard Seifried, Uwe Platzbecker, Hind Medyouf, Manuel Grez, Jörn Lausen,

A network of lineage-specific transcription factors and microRNAs tightly regulates differentiation of hematopoietic stem cells along the distinct lineages. Deregulation of this regulatory network contributes to impaired lineage fidelity and leukemogenesis. We found that the hematopoietic master regulator RUNX1 controls the expression of certain microRNAs, of importance during erythroid/megakaryocytic differentiation. ... Read more >>

PLoS Genet (PLoS genetics)
[2016, 12(3):e1005946]

Cited: 11 times

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The truncated RUNX1/ETO activates VLA-4-dependent adhesion and migration of hematopoietic progenitor cells.

Kanagaraju Ponnusamy, Linping Chen-Wichmann, Olga N Kuvardina, Jörn Lausen, Reinhard Henschler, Christian Wichmann,

Haematologica (Haematologica)
[2014, 99(12):e253-6]

Cited: 6 times

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One-step radiosynthesis of 4-nitrophenyl 2-[(18) F]fluoropropionate ([(18) F]NFP); improved preparation of radiolabeled peptides for PET imaging.

Mohammad B Haskali, Peter D Roselt, John A Karas, Wayne Noonan, Christian W Wichmann, Andrew Katsifis, Rodney J Hicks, Craig A Hutton,

The versatile (18) F-labeled prosthetic group, 4-nitrophenyl 2-[(18) F]fluoropropionate ([(18) F]NFP), was synthesized in a single step in 45 min from 4-nitrophenyl 2-bromopropionate, with a decay corrected radiochemical yield of 26.2% ± 2.2%. Employing this improved synthesis of [(18) F]NFP, [(18) F]GalactoRGD - the current 'gold standard' tracer for imaging the expression of ... Read more >>

J Labelled Comp Radiopharm (Journal of labelled compounds & radiopharmaceuticals)
[2013, 56(14):726-730]

Cited: 8 times

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Fully automated synthesis and coupling of [(18) F]FBEM to glutathione using the iPHASE FlexLab module.

Uwe Ackermann, Lucie Plougastel, Christian Wichmann, Yit Wooi Goh, Shinn Dee Yeoh, Stan S Poniger, Henri J Tochon-Danguy, Andrew M Scott,

Site-specific radiolabelling of peptides or antibodies using [(18) F]FBEM is often preferred over non-site-specific radiolabelling with [(18) F]SFB because it does not affect the affinity of the antibody to its target. Unfortunately, the synthesis of [(18) F]FBEM and its conjugation to thiol containing macromolecules requires some manual intervention, which leads ... Read more >>

J Labelled Comp Radiopharm (Journal of labelled compounds & radiopharmaceuticals)
[2014, 57(2):115-120]

Cited: 6 times

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From determinants of RUNX1/ETO tetramerization to small-molecule protein-protein interaction inhibitors targeting acute myeloid leukemia.

Alexander Metz, Julia Schanda, Manuel Grez, Christian Wichmann, Holger Gohlke,

We identified the first small-molecule protein-protein interaction inhibitors of RUNX1/ETO tetramerization applying structure-based virtual screening guided by predicted hot spots and pockets in the interface. A 3D similarity screening revealed specific hot spot mimetics, one of which prevents the proliferation of RUNX1/ETO-dependent SKNO-1 cells at low micromolar concentration. Using solely ... Read more >>

J Chem Inf Model (Journal of chemical information and modeling)
[2013, 53(9):2197-2202]

Cited: 10 times

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Interference with RUNX1/ETO leukemogenic function by cell-penetrating peptides targeting the NHR2 oligomerization domain.

Yvonne Bartel, Manuel Grez, Christian Wichmann,

The leukemia-associated fusion protein RUNX1/ETO is generated by the chromosomal translocation t(8;21) which appears in about 12% of all de novo acute myeloid leukemias (AMLs). Essential for the oncogenic potential of RUNX1/ETO is the oligomerization of the chimeric fusion protein through the nervy homology region 2 (NHR2) within ETO. In ... Read more >>

Biomed Res Int (BioMed research international)
[2013, 2013:297692]

Cited: 4 times

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Molecular targeting of aberrant transcription factors in leukemia: strategies for RUNX1/ETO.

Christian Wichmann, Manuel Grez, Jörn Lausen,

Malignant cell transformation is caused by mutations in distinct key regulatory genes involved in cell growth, apoptosis, senescence and differentiation. Particularly in human leukemia, chromosomal translocations involving crucial hematopoietic transcription factors are frequently causally linked to the disease. Transcription factors commonly have a modular structure, comprising distinct domains for DNA- ... Read more >>

Curr Drug Targets (Current drug targets)
[2010, 11(9):1181-1191]

Cited: 5 times

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Dimer-tetramer transition controls RUNX1/ETO leukemogenic activity.

Christian Wichmann, Yvonne Becker, Linping Chen-Wichmann, Vitali Vogel, Anna Vojtkova, Julia Herglotz, Sandra Moore, Joachim Koch, Jörn Lausen, Werner Mäntele, Holger Gohlke, Manuel Grez,

RUNX1/ETO, the fusion protein resulting from the chromosomal translocation t(8;21), is one of the most frequent translocation products in acute myeloid leukemia. Several in vitro and in vivo studies have shown that the homo-tetramerization domain of ETO, the nervy homology region 2 (NHR2), is essential for RUNX1/ETO oncogenic activity. We ... Read more >>

Blood (Blood)
[2010, 116(4):603-613]

Cited: 28 times

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