Hauptinhalt

Publikationen der AG Hantschel

  • 2024

    Leske, I.B. und Hantschel, O. (2024) The e13a3 (b2a3) and e14a3 (b3a3) BCR::ABL1 isoforms are resistant to asciminib. Leukemia. https://doi.org/10.1038/s41375-024-02314-7.

    Leyte-Vidal, A., Garrido Ruiz, D., DeFilippis, .A., Leske, IB.,Rea, D., Phan, S., Miller, KB., Hu, F., Mase, A., Shan, Y., Hantschel, O., Jacobson, MP. und Shah, NP. (2024) BCR::ABL1 Kinase N-lobe Mutants Confer Moderate to High Degrees of Resistance to Asciminib. Blood. https://doi.org/10.1182/blood.2023022538.

    Dinh-Fricke, AV. und Hantschel, O. (2024) Improving the pharmacokinetics, biodistribution and plasma stability of monobodies. Frontiers in  Pharmacology Volume 15 - 2024.

    Hantschel, O. (2024) The druggability of SH2 domains unmasked. Nature Chemical Biology, 20, pages 271–272.

  • 2023

  • 2022

    Schmidt, N., Abendroth, F., Vázquez, O. and Hantschel, O. (2022) Synthesis of the L- and D-SH2 domain of the leukaemia oncogene Bcr-Abl. RSC Chemical Biology, DOI: 10.1039/d2cb00108j.

  • 2021

    Valent, P., Orfao, A., Kubicek, S., Staber, P., Haferlach, T., Deininger, M., Kollmann, K., Lion, T., Virgolini, I., Winter, G., Hantschel, O., Kenner, L., Johannes Zuber, J., Grebien, F., Moriggl, R., Hörmann, G., Hermine, O., Andreeff, M., Bock, C., Mughal, T., Constantinescu, S., Kralovics, R., Sexl, V., Skoda, R., Superti-Furga, G. and Jäger, U. (2021) Precision Medicine in Hematology 2021: Definitions, Tools, Perspectives and Open Issues, HemaSphere, 5(3), e536.

    Mian, A.A., Haberbosch, I., Khamaisie, H., Agbarya, A., Pietsch, L., Eshel, E., Najib, D., Chiriches, C., Ottmann, O.G., Hantschel, O., Biondi, R.M., Ruthardt, M. and Mahajna, J. (2021) Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1 T315I and BCR-ABL1 T315I-E255K. Annals of Hermatology, 100, pages 2023–2029 (2021).

  • 2020

    La Sala, G., Michiels, C., Kukenshöner, T., Brandstoetter, T., Maurer, B., Koide, A., Lau, K., Pojer, F., Koide, S., Sexl, V., Dumoutier, L. and Hantschel, O. (2020) Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains. Nat. Commun., 11(1), 4115.

    Duarte, D.P., Lamontanara, A.J., La Sala, G., Jeong, S., Sohn, Y.-K., Panjkovich, A., Georgeon, S., Kükenshöner, T., Marcaida, M.J., Pojer, F., De Vivo, M., Svergun, D., Kim, H.-S., Dal Peraro, M. and Hantschel, O. (2020) Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms. Nat. Commun., 11:2319.

    Hantschel O. (2020) CDK6 degradation hits Ph+ ALL hard. Blood, 135(18), 1512-1514.

    Hantschel, O., Biancalana, M. and Koide, S. (2020) Monobodies as enabling tools for structural and mechanistic biology. Curr. Opin. Struct. Biol., 60, 167-174.

  • 2019

    Taft, J., Georgeon, S., Allen, C., Reckel, S., DeSautelle, J., Hantschel, O., Georgiou, G. and Iverson, B.L. (2019) A Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity. ACS Chem. Biol., 14(9), 1888-1895.

    Schmit, N.E., Neopane, K. and Hantschel, O. (2019). Targeted protein degradation through cytosolic delivery of monobody binders using bacterial toxins. ACS Chem. Biol., 14(5), 916-924.

    Luong-Gardiol, N., Siddiqui, I., Pizzitola, I., Jeevan-Raj, B., Charmoy, M., Huang, Y., Irmisch, A., Curtet, S., Angelov, G.S., Danilo, M., Juilland, M., Bornhauser, B., Thome, M., Hantschel, O., Chalandon, Y., Cazzaniga, G., Bourquin, J.-P., Huelsken, J. and Held, W. (2019). γ-catenin-dependent signals maintain BCR-ABL1+ B cell acute lymphoblastic leukemia, Cancer Cell, 35(4), 649-663.

    Mian, A.A., Baumann, I., Liebermann, M., Grebien, F., Superti-Furga, G., Ruthardt, M., Ottman, O.G. and Hantschel, O. (2019) The Phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis. Leukemia 33(9), 2319-2323.

  • 2018

    Sonti, R., Hertel-Hering, I., Lamontanara, A., Hantschel, O. and Grzesiek, S. (2018) ATP site ligands determine the assembly state of the Abelson kinase regulatory core via the activation loop conformation. J. Am. Chem. Soc., 140(5), 1863-1869.

    Kim, D.I., Cutler, J.A., Na,C.H., Reckel, S., Renuse, S., Madugundu, A.K., Tahir, R., Goldschmidt, H., Reddy, K.L., Huganir, R.L., Wu, X., Hantschel, O. and Pandey, A. (2018) BioSITe: A novel method for direct detection of site specific biotinylation. J. Proteome Res., 17(2), 759-769.

    Byrgazov, K., Lucini, C.B., Valent, P., Hantschel, O. and Lion, T. (2018) BCR-ABL1 Compound Mutants Display Differential and Dose-Dependent Responses to Ponatinib, Haematologica, 103(1), e10-e12

  • 2017

    Reckel, S., Gehin, C., Tardivon, D., Georgeon, S., Kükenshöner, T., Löhr, F., Koide, A., Buchner, L., Panjkovich, A., Reynaud, A., Pinho, S., Gerig, B., Svergun, D., Pojer, F., Güntert, P., Dötsch, V., Koide, S., Gavin, A.-C. and Hantschel, O. (2017) Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase. Nat. Commun., 8(1), 2101.

    Saarbach, J., Lindberg, E., Folliet, S., Georgeon, S., Hantschel, O. and Winssinger, N. (2017) Kinase-templated abiotic reaction. Chem. Sci., 8, 5119-5125.

    Bryan, L.C., Weilandt, D., Bachmann, L., Kilic, S., Lechner, C., Odermatt, P., Fantner, G., Georgeon, S., Hantschel, O., Hatzimanikatis, V. and Fierz, B. (2017). Single-molecule kinetic analysis of HP1-chromatin binding reveals a dynamic network of histone modification and DNA interactions. Nucleic Acids Res.,  45(18), 10504-10517.

    Zhang, H., Means, S., Reister Schultz, A., Watanabe-Smith, K., Medeiros, B.C., Bottomly, D., Wilmot, B., McWeeney, S.K., Kükenshöner, T., Hantschel, O and Tyner, J.W. (2017) Unpaired, extracellular cysteine mutations of CSF3R mediate gain or loss of function. Cancer Res., 77(16), 4258-4267.

    Kükenshöner, T., Schmit, N.E., Bouda, E., Sha, F., Pojer, F., Koide, A., Seeliger, M., Koide, S. and Hantschel, O. (2017) Potent Targeting of SH2 Domain-Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies, J. Mol. Biol., 429(9), 1364-1380

    Reckel, S., Hamelin, R., Georgeon, S., Armand, F., Jolliet, Q., Chiappe, D., Moniatte, M and Hantschel, O. (2017) Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics, Leukemia, 31(7), 1502-1512.

    Seo, H.-D., Lee, J.-J., Kim, Y. J., Hantschel, O., Lee, S.-G. and Kim, H.-S. (2017) Alkaline phosphatase-fused repebody as a new format of immuno-reagent for an immunoassay, Anal. Chim. Acta, 950, 184-191.

    Byrgazov, K., Gorna, M., Hoermann, G., König, M., Ulreich, R., Benesch, M., Strenger, V., Lackner, H., Schwinger, W., Sovinz, P., Haas, O.H., van den Heuvel-Eibrink, M., Niemeyer, C.M., Hantschel, O., Valent, P., Superti-Furga, G., Urban, C., Dworzak, M.N. and Lion, T. (2017). NDEL1-PDGFRB Fusion Gene in a Myeloid Malignancy with Eosinophilia Associated with Resistance to Tyrosine Kinase Inhibitors, Leukemia, 31(1), 237-240.

    Reckel S. and Hantschel O. (2017) Bcr-Abl: One kinase, two isoforms, two diseases. Oncotarget, 8(45), 78257-78258.

    Hantschel O. (2017) Monobodies as possible next-generation protein therapeutics - A perspective. Swiss Medical Weekly, 147, w14545.

    Hantschel O. and Ottmann, O.G. (2017) Allosteric kinase inhibitors. Themenheft "Neue Substanzen und Wirkprinzipien". Der Onkologe, 23(8), 626-631.

  • 2016

    La Sala, G., Riccardi, L., Gaspari, R., Cavalli, A., Hantschel, O. and De Vivo, M. (2016) The HRD motif as the central hub of the signaling network for activation loop autophosphorylation in Abl kinase, J. Chem. Theory Comput., 12(11), 5563-5574.

    Wojcik, J., Lamontanara, A.J., Grabe, G., Koide, A., Akin, L., Gerig, B., Hantschel, O. and Koide, S. (2016). High-affinity monobody inhibitors directed to the SH2-kinase interface of Bcr-Abl, J. Biol. Chem., 291(16), 8836-8847.

    Dasgupta, Y., Koptyra, M., Hoser, G., Kantekure, K., Roy, D., Gornicka, B., Nieborowska-Skorska, M., Bolton Gillespie, E., Cerny-Reiterer, S., Müschen, M., Valent, P., Wasik, M.A., Richardson, C., Hantschel, O., van der Kuip, H. Stoklosa, T., and Skorski, T. (2016). Normal ABL1 is a Tumor Suppressor and Therapeutic Target in Leukemias Expressing Oncogenic ABL1 kinases, Blood, 127(17), 2131-2143.

    Maxson, J.E., Abel, M.L., Wang, J., Deng, X., Reckel, S., Luty, S.B., Sun, H., Gorenstein, J., Hughes, S., Bottomly, D., Wilmot, B., McWeeney, S.K., Radich, J., Hantschel, O., Middleton, R.E., Gray, N.S., Druker, B.J., Tyner, J.W. (2016) Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis. Cancer Res., 76(1), 127-138.

    Hantschel O. and Fierz, B. (2016) 2016 International Symposium on Chemical Biology of the NCCR Chemical Biology, Campus Biotech, Geneva 13-15.1.2016. Chimia, 70(3), 215-219.

  • 2015

    Lorenz, S., Deng, P., Hantschel, O., Superti-Furga, G. and Kuriyan, J. (2015). Crystal structure of an SH2-kinase construct of c-Abl and effect of the SH2 domain on kinase activity, Biochem. J., 468(2), 283-291.

    Reckel S. and Hantschel O. (2015) Kinase Regulation in Mycobacterium tuberculosis: Variations on a Theme. Structure, 23(6), 975-976.

    Hantschel, O. (2015). Targeting BCR-ABL and JAK2 in Ph+ ALL. Blood, 125(9), 1362-1363.

    Hantschel, O. (2015) Unexpected off-targets and paradoxical pathway activation by kinase inhibitors. ACS Chem. Biol., 10(1), 234-45.

  • 2014

    Lamontanara, A.J., Georgeon, S., Tria, G., Svergun, D.I. and Hantschel, O. (2014). The SH2 domain of ABL kinases regulates kinase autophosphorylation by controlling activation loop accessibility, Nat. Commun. 5, 5470.

    Mahul-Mellier, A.-L., Fauvet, B., Gysbers, A., Dikiy, I., Oueslati, A., Georgeon, S., Lamontanara, A.J., Bisquertt, A., Eliezer, D., Masliah, E., Halliday, G., Hantschel, O. and Lashuel, H.A. (2014). c-Abl phosphorylates α-syn and regulates its degradation, implication for α-syn clearance and contribution to the pathogenesis of Parkinson’s Disease. Hum. Mol. Genet. 23(11), 2858-2879.

    Zhou, T., Georgeon, S., Moser, R., Moore, D.J., Caflisch, A., Hantschel, O. (2014). Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348) Leukemia. 28, 404–407.

    De Keersmaecker, K.*, Porcu, M.*, Cox, L., Girardi, T., Vandepoel, R., Girardi, T., Gielen, G., Mentens, N., Bennett, K.L. and Hantschel, O. (2014). NUP214-ABL1 mediated cell proliferation in T-cell acute lymphoblastic leukemia is dependent on the LCK kinase and various interacting proteins. Haematologica, 99(1), 85-93.

  • 2013

    Sha, F.*, Gencer, E.B.*, Georgeon, S., Koide, A., Yasui, N., Koide, S. and Hantschel, O. (2013). Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains. Proc. Natl. Acad. Sci. USA, 110(37), 14924-14929.

    Lamontanara, A. J., Gencer, E. B., Kuzyk, O. and Hantschel, O. (2013) Mechanisms of resistance to BCR-ABL and other kinase inhibitors. Biochim. Biophys. Acta, 1834, 1449-1459.

  • 2012

    Hopkins, S.*, Linderoth, E.*, Hantschel, O., Suarez-Henriques, P., Pilia, G., Kendrick, H., Smalley, M.J., Superti-Furga, G. and Ferby, I. (2012). Mig6 is a sensor of EGF receptor inactivation that directly activates c-Abl to induce apoptosis during epithelial homeostasis. Dev. Cell, 23(3), 547-559.

    Hantschel, O.*, Warsch, W.*, Eckelhart, E.*, Kaupe, I., Grebien, F., Wagner, K.-U., Superti-Furga, G. and Sexl, V. (2012). BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia. Nat. Chem. Biol., 8(3), 285-293.

    Hantschel, O. and Superti-Furga, G. (2012). Cell biology: A key driver of therapeutic innovation. J. Cell Biol., 199(4), 571-575.

    Hantschel, O. (2012). Structure, regulation, signaling and targeting of Abl kinases in cancer. Genes&Cancer, 3(5-6), 436-446.

    Hantschel, O., Grebien, F. and Superti-Furga, G. (2012). The growing arsenal of ATP-competitive and allosteric inhibitors of BCR-ABL. Cancer Res., 72(19), 4890-4895.

    Hantschel, O. (2012). Allosteric Bcr-Abl inhibitors in Ph+ acute lymphoblastic leukemia: novel opportunities for drug combinations to overcome resistance. Haematologica, 97(2), 157-159.

    Valent, P., Gastl, G., Geissler, K., Greil, R., Hantschel, O., Lang, A., Linkesch, W., Lion, T., Petzer, A.L., Pittermann, E., Pleyer, L., Thaler, J. and Wolf, D. (2012). Nilotinib as Frontline and Second-Line Therapy in Chronic Myeloid Leukemia: Open Questions. Crit. Rev. Oncol. Hemat., 82(3), 370-377.

  • 2011

    Grebien, F. *, Hantschel, O. *, Wojcik, J., Kaupe, I., Kovacic, B., Wyrzucki, A. M., Gish, G. D., Cerny-Reiterer, S., Koide, A., Beug, H., Pawson, T., Valent, P., Koide, S. and Superti-Furga, G. (2011). Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis. Cell, 147(2), 306–319.

    Hantschel, O., Grebien, F. and Superti-Furga, G. (2011). Targeting allosteric regulatory modules in oncoproteins: “Drugging the Undruggable”. Oncotarget, 2(11), 828-829.

  • 2010

    Sherbenou, D.W.*, Hantschel, O.*, Kaupe, I., Willis, S., Bumm, T., Turaga, L., Lange, T., Dao, K.H., Press, R.D., Superti-Furga, G., Druker, B.J. and Deininger, M.W. (2010). BCR-ABL SH3-SH2 domain mutations in chronic myeloid leukemia patients on imatinib, Blood, 116(17), 3278-3285.

    Wojcik, J., Hantschel, O., Grebien, F., Kaupe, I., Bennett, K.L., Barkinge, J., Jones, R.B., Koide, A., Superti-Furga, G. and Koide, S. (2010). A potent highly specific FN3 monobody inhibitor of the Abl SH2 domain. Nat. Struct. Mol. Biol., 17(4), 519-527.

    Rix, U., Remsing Rix, L.L., Terker, A.S., Fernbach, N.V., Hantschel, O., Planyavsky, M., Breitwieser, F.P., Herrmann, H., Colinge, J., Bennett, K.L., Augustin, M., Till, J.H. Heinrich, M.C., Valent, P. and Superti-Furga, G. (2010). A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells. Leukemia, 24(1), 44-50.

  • 2009

    Brehme, M.*, Hantschel, O.*, Colinge, J., Kaupe, I., Planyavsky, M., Koecher, T., Mechtler, K., Bennett, K.L. and Superti-Furga, G. (2009). Charting the molecular network of the drug target Bcr-Abl. Proc. Natl. Acad. Sci. USA, 106(18), 7414-7419.

    Remsing Rix, L.L., Rix, U., Colinge, J., Hantschel, O., Bennett, K.L., Stranzl, T., Müller, A., Valent, P., Augustin, M., Till, J. and Superti-Furga, G. (2009). Global target profile of the kinase inhibitor bosutinib in chronic myeloid leukemia. Leukemia, 23(3), 477-485.

    Winger, J.A., Hantschel, O, Superti-Furga, G. and Kuriyan, J. (2009) The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2). BMC Structural Biology 9(1), 7.

  • 2008

    De Keersmaecker, K., Versele, M., Cools, J., Superti-Furga, G. and Hantschel, O. (2008). Intrinsic differences between the catalytic properties of the oncogenic NUP214-ABL1 and BCR-ABL1 fusion protein kinases. Leukemia, 22(12), 2208-2216.

    Filippakopoulos, P.*, Kofler, M.*, Hantschel, O.*, Gish, G.D.*, Grebien, F., Salah, E., Neudecker, P., Kay, L.E., Turk, B.E., Superti-Furga, G., Pawson, T. and Knapp, S. (2008). Structural Coupling of SH2-Kinase Domains Links Fes and Abl Substrate Recognition and Kinase Activation. Cell, 134(5), 793-803.

    Hantschel, O.*, Gstoettenbauer, A.*, Colinge, J., Kaupe, I., Bilban, M., Burkard, T.R., Valent, P. and Superti-Furga, G. (2008). The chemokine IL-8 and the surface activation protein CD69 are markers for Bcr-Abl activity in CML. Molecular Oncology, 2(3), 272-281.

    Soulat, D., Bürckstümmer, T., Westermayer, S., Goncalves, A., Bauch, A., Stefanovic, A., Hantschel, O., Bennett, K.L., Decker, T. and Superti-Furga, G. (2008). The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J., 27(15), 2135-2146.

    Sherbenou, D.W., Hantschel, O., Turaga, L., Kaupe, I., Willis, S., Bumm, T., Press, R.D., Superti-Furga, G., Druker, B.J. and Deininger, M.W. (2008). Characterization of BCR-ABL deletion mutants from patients with chronic myeloid leukemia. Leukemia, 22(6), 1184-1190.

    Hantschel, O., Rix, U. and Superti-Furga, G. (2008). Target spectrum of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib. Leuk. Lymphoma, 49(4), 615-619.

  • 2007

    Rix, U.*, Hantschel, O.*, Dürnberger, G., Remsing Rix, L.L., Planyavsky, M., Fernbach, N.V., Kaupe, I., Bennett, K.L., Valent, P., Colinge, J., Köcher, T. and Superti-Furga, G. (2007). Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib reveal novel kinase and non-kinase targets, Blood, 110(12), 4055-4063.

    Hantschel, O.*, Rix, U.*, Schmidt, U.*, Bürckstümmer, T.*, Kneidinger, M., Schütze, G., Bennett, K.L., Ellmeier, W., Valent, P. and Superti-Furga, G. (2007). The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc. Natl. Acad. Sci. USA, 104(33), 13283-13288.

    Mughal, T., Cortes, J., Cross, N. C., Donato, N., Hantschel, O., Jabbour, E., Kantarjian, H., Melo, J. V., Skorski, T., Silver, R. T., and Goldman, J. M. (2007). Chronic myeloid leukemia - some topical issues. Leukemia, 21(7), 1347-1352.

  • 2006

    Bürckstümmer, T., Bennett, K. L., Preradovic, A., Schütze, G., Hantschel, O., Superti-Furga, G. and Bauch, A. (2006). An efficient tandem affinity purification procedure for the characterization of protein complexes in mammalian cells. Nature Methods, 3(12), 1013-1019.

    Nagar, B., Hantschel, O., Seeliger, M., Davies, J.M., Weis, W. I., Superti-Furga, G. and Kuriyan, J. (2006). Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase, Mol. Cell, 21, 787-798.

  • 2005

    Wiesner, S., Hantschel, O., Mackereth, C.D., Superti-Furga, G. and Sattler, M. (2005). NMR Assignment Reveals an alpha-Helical Fold for the F-Actin Binding Domain of Human Bcr-Abl/c-Abl. J. Biomol. NMR, 32(4), 335.

    Hantschel, O.*, Wiesner, S.*, Güttler, T., Mackereth, C. D., Remsing Rix, L.L., Mikes, Z., Dehne, J., Görlich, D., Sattler, M. and Superti-Furga, G. (2005). Structural basis for cytoskeletal association of Bcr-Abl/c-Abl. Mol. Cell, 19(4), 461-473.

    Hantschel, O. and Superti-Furga, G. (2005). Mechanisms of activation of Abl family kinases, in: Abl Family Kinases in Development and Disease, Landes Biosciences

  • 2004

    Ellenrieder, A. D., Kremer, W., Kattenbeck, B., Hantschel, O., Horn, G., Kalbitzer, H. R. and Modrow, S. (2004). The central domain of the matrix protein of HIV-1: influence on protein structure and virus infectivity. Biol. Chem. 385, 303-313.

    Hantschel, O. (2004). Regulation der Tyrosinkinasen c-Abl/Bcr-Abl. BIOspektrum 10, 514-517.

    Hantschel, O. and Superti-Furga, G. (2004). Regulation of the c-Abl and Bcr-Abl Tyrosine Kinases. Nature Rev. Mol. Cell Biol. 5(1), 33-44.

  • 2003

    Nagar, B.*, Hantschel, O.*, Young, M. A., Scheffzek, K., Veach, D., Bornmann, W., Clarkson, B., Superti-Furga, G., and Kuriyan, J. (2003). Structural Basis for the Autoinhibition of c-Abl Tyrosine Kinase. Cell 112(6), 859-871.

    Hantschel, O.*, Nagar, B.*, Guettler, S., Kretzschmar, J., Dorey, K., Kuriyan, J., and Superti-Furga, G. (2003). A Myristoyl/Phosphotyrosine Switch Regulates c-Abl. Cell 112(6), 845-