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3. Prolonged survival in patients >= 60 years with first relapsed/refractory acute myeloid leukemia treated with vosaroxin plus cytarabine vs placebo plus cytarabine: Results from the phase 3 VALOR study

Author

Krug, U, Ravandi, F, Ritchie, EK, Sayar, H, Lancet, JE, Craig, MD, Vey, N, Strickland, SA, Schiller, GJ, Jabbour, E, Erba, HP, Pigneux, A, Horst, H-A, Recher, C, Klimek, VM, Cortes, J, Roboz, GJ, Craig, AR, Fox, JA, Ward, R, Smith, JA, Acton, G, Mehta, C, Kantarjian, HM, and Stuart, RK

Published
2015

4. Age, not therapy intensity, determines outcomes of adults with acute myeloid leukemia

Author

Büchner, T, Krug, U O, Peter Gale, R, Heinecke, A, Sauerland, M C, Haferlach, C, Schnittger, S, Haferlach, T, Müller-Tidow, C, Stelljes, M, Mesters, R M, Serve, H L, Braess, J, Spiekermann, K, Staib, P, Grüneisen, A, Reichle, A, Balleisen, L, Eimermacher, H, Giagounidis, A, Rasche, H, Lengfelder, E, Görlich, D, Faldum, A, Köpcke, W, Hehlmann, R, Wörmann, B J, Berdel, W E, and Hiddemann, W

Published
2016
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5. Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia

Author

Krug, U, Berdel, W E, Gale, R P, Haferlach, C, Schnittger, S, Müller-Tidow, C, Braess, J, Spiekermann, K, Staib, P, Beelen, D, Serve, H, Schliemann, C, Stelljes, M, Balleisen, L, Maschmeyer, G, Grüneisen, A, Eimermacher, H, Giagounidis, A, Rasche, H, Hehlmann, R, Lengfelder, E, Thiel, E, Reichle, A, Aul, C, Ludwig, W-D, Kern, W, Haferlach, T, Köpcke, W, Görlich, D, Sauerland, M C, Heinecke, A, Wörmann, B J, Hiddemann, W, and Büchner, T

Published
2016
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6. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia

Author

Müller-Tidow, C, Tschanter, P, Röllig, C, Thiede, C, Koschmieder, A, Stelljes, M, Koschmieder, S, Dugas, M, Gerss, J, Butterfaß-Bahloul, T, Wagner, R, Eveslage, M, Thiem, U, Krause, S W, Kaiser, U, Kunzmann, V, Steffen, B, Noppeney, R, Herr, W, Baldus, C D, Schmitz, N, Götze, K, Reichle, A, Kaufmann, M, Neubauer, A, Schäfer-Eckart, K, Hänel, M, Peceny, R, Frickhofen, N, Kiehl, M, Giagounidis, A, Görner, M, Repp, R, Link, H, Kiani, A, Naumann, R, Brümmendorf, T H, Serve, H, Ehninger, G, Berdel, W E, and Krug, U

Published
2016
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7. P558: GERMAN AMLCG-SURVIVORSHIP STUDY – SOMATIC LONG-TERM CONSEQUENCE OF AML AND ITS THERAPY: FROM HEART TO KIDNEY.

Author

Moret, A. S., primary, Telzerow, E., additional, Sauerland, C., additional, Rothenberg-Thurley, M., additional, Mumm, F. H. A., additional, Braess, J., additional, Wörmann, B., additional, Krug, U., additional, Berdel, W. E., additional, Hiddemann, W., additional, Spiekermann, K., additional, Heußner, P., additional, Kraywinkel, K., additional, Görlich, D., additional, and Metzeler, K. H., additional

Published
2022
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8. P479: DNA METHYLATION PROFILING REFINES THE PROGNOSTIC CLASSIFICATION OF ACUTE MYELOID LEUKEMIA PATIENTS TREATED WITH INTENSIVE CHEMOTHERAPY

Author

Vosberg, S., primary, Ohnmacht, A., additional, Moser, C., additional, Arneth, A., additional, Jurinovic, V., additional, Metzeler, K. H., additional, Sauerland, M. C., additional, Görlich, D., additional, Berdel, W. E., additional, Braess, J., additional, Amler, S., additional, Krug, U., additional, Hiddemann, W., additional, Spiekermann, K., additional, Oakes, C. C., additional, Menden, M. P., additional, Herold, T., additional, and Greif, P. A., additional

Published
2022
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9. S301: GERMAN AMLCG-SURVIVORSHIP STUDY: QUALITY OF LIFE AND LIFE SATISFACTION IN AML LONG-TERM SURVIVORS

Author

Telzerow, E., primary, Görlich, D., additional, Sauerland, C., additional, Moret, A. S., additional, Rothenberg-Thurley, M., additional, Mumm, F. H. A., additional, Amler, S., additional, Berdel, W. E., additional, Wörmann, B., additional, Krug, U., additional, Braess, J., additional, Heussner, P., additional, Hiddemann, W., additional, Spiekermann, K., additional, and Metzeler, K. H., additional

Published
2022
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10. P416: CLONAL HEMATOPOIESIS IS COMMON IN AML LONG-TERM SURVIVORS AND MAY ASSOCIATE WITH DIABETES AND SECONDARY NEOPLASIAS, BUT NOT OTHER HEALTH OUTCOMES

Author

Krauß, S. M., primary, Telzerow, E., additional, Moret, A. S., additional, Richter, D., additional, Rothenberg-Thurley, M., additional, Görlich, D., additional, Sauerland, M. C., additional, Berdel, W. E., additional, Wörmann, B., additional, Krug, U., additional, Braess, J., additional, Heussner, P., additional, Enard, W., additional, Hiddemann, W., additional, Spiekermann, K., additional, Platzbecker, U., additional, and Metzeler, K. H., additional

Published
2022
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18. Structures of 2-Hydroxyisobutyric Acid-CoA ligase reveal determinants of substrate specificity and describe a multi-conformational catalytic cycle

Author

Zahn, M., Kurteva-Yaneva, Nadya, Schuster, Judith, Krug, U., Georgi, Tina, Müller, Roland, Rohwerder, Thore, Sträter, N., Zahn, M., Kurteva-Yaneva, Nadya, Schuster, Judith, Krug, U., Georgi, Tina, Müller, Roland, Rohwerder, Thore, and Sträter, N.

Abstract

2-Hydroxyisobutyric acid (2-HIBA) is a biomarker of adiposity and associated metabolic diseases such as diabetes mellitus. It is also formed in the bacterial degradation pathway of the fuel oxygenate methyl tert-butyl ether (MTBE), requiring thioesterification with CoA prior to isomerization to 3-hydroxybutyryl-CoA by B12-dependent acyl-CoA mutases. Here, we identify the adenylating enzymes superfamily member 2-HIBA-CoA ligase (HCL) in the MTBE-degrading bacterium Aquincola tertiaricarbonis L108 by knockout experiments. To characterize this central enzyme of 2-HIBA metabolism, ligase activity kinetics of purified HCL and its X-ray crystal structures were studied. We analyzed the enzyme in three states, which differ in the orientation of the two enzyme domains. A 154° rotation of the C-terminal domain accompanies the switch from the adenylate- into the thioester-forming state. Furthermore, a third conformation was obtained, which differs by 50° and 130° from the adenylation and thioesterification states, respectively. Phylogenetic and structural analysis reveals that HCL defines a new subgroup within phenylacetate-CoA ligases (PCLs) thus far described to exclusively accept aromatic acyl substrates. In contrast, kinetic characterization clearly demonstrated that HCL catalyzes CoA activation of several aliphatic short-chain carboxylic acids, preferentially 2-HIBA. Compared to the classical PCL representatives PaaK1 and PaaK2 of Burkholderia cenocepacia J2315, the acyl binding pocket of HCL is significantly smaller and more polar, due to unique active-site residues Y164 and S239 forming H-bonds with the OH-group of the acyl substrate moiety. Furthermore, HCL and PaaK topologies illustrate the evolutionary steps leading from a homodimeric to the fused monomeric core fold found in other ligases.

Published
2019

20. Key Data Elements in Myeloid Leukemia

Author

Varghese, J., Holz, C., Neuhaus, P., Bernardi, M., Boehm, A., Ganser, A., Gore, S., Heaney, M., Hochhaus, A., Hofmann, W.K., Krug, U., Muller-Tidow, C., Smith, A., Weltermann, A., Witte, T.J.M. de, Hehlmann, R., and Dugas, M.

Subjects
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Abstract

Contains fulltext : 172875.pdf (Publisher’s version ) (Open Access) Data standards consisting of key data elements for clinical routine and trial documentation harmonize documentation within and across different health care institutions making documentation more efficient and improving scientific data analysis. This work focusses on the field of myeloid leukemia (ML), where a semantic core of common data elements (CDEs) in routine and trial documentation is established by automatic UMLS-based form analysis of existing documentation models. These CDEs (n = 227) were initially reviewed and commented by leukemia experts before they were systematically surveyed by an international voting process through seven hematologists of four countries. The total agreement score was 86%. 116 elements (51%) of these share an agreement score of 100%. This work generated CDEs with language-independent semantic codes and international clinical expert review to build a first approach towards an international data standard for ML. A first version of the CDE list is implemented in the data standard Operational Data Model and additional other data formats for reuse in different medical information systems.

Published
2016

21. The addition of sorafenib to standard AML treatment results in a substantial reduction in relapse risk and improved survival : Updated results from long-term follow-up of the randomized-controlled SORAML trial

Author

Röllig, C., Serve, H., Hüttmann, Andreas, Noppeney, Richard, Müller-Tidow, Carsten, Krug, U., Baldus, C. D., Brandts, C. H., Kunzmann, V., Einsele, H., Krämer, A., Schäfer-Eckart, K., Neubauer, A., Burchert, A., Giagounidis, A., Krause, S. W., Mackensen, A., Aulitzky, W., Herbst, R., Hänel, M., Kiani, A., Frickhofen, N., Kullmer, J., Kaiser, U., Link, H., Geer, T., Reichle, A., Junghanß, C., Bornhäuser, M., Schaich, M., Thiede, C., Schetelig, J., Kramer, M., Berdel, W. E., Ehninger, G., and Studienallianz Leukämie (SAL)

Subjects
Medizin
Published
2018

22. Allogeneic hematopoietic stem cell transplantation (HSCT) beyond first complete remission (CR) in patients with acute myeloid leukemia (AML) : Results from the AMLCG1999 trial

Author

Evers, G., Beelen, Dietrich W., Braess, J., Sauerland, Maria Cristina, Kolb, H. J., Reichle, A., Holler, E., Schwerdtfeger, R., Arnold, R., Scheid, C., Krug, U., Müller-Tidow, C., Schliemann, C., Mikesch, J.-H., Lenz, G., Wörmann, B. J., Hiddemann, W., Berdel, W. E., and Stelljes, M.

Subjects
Medizin
Published
2018

23. S1614 CHROMOSOMAL ABNORMALITIES DETERMINE OUTCOME IN NPM1MUT/FLT3-ITDNEG/LOW ACUTE MYELOID LEUKEMIA

Author

Angenendt, L., primary, Röllig, C., additional, Montesinos, P., additional, Martínez-Cuadrón, D., additional, Barragan, E., additional, García, R., additional, Botella, C., additional, Martínez, P., additional, Ravandi, F., additional, Kadia, T., additional, Kantarjian, H.M., additional, Cortes, J., additional, Juliusson, G., additional, Lazarevic, V., additional, Höglund, M., additional, Lehmann, S., additional, Recher, C., additional, Pigneux, A., additional, Bertoli, S., additional, Dumas, P.-Y., additional, Dombret, H., additional, Preudhomme, C., additional, Micol, J.-B., additional, Terré, C., additional, Ráčil, Z., additional, Novák, J., additional, Žák, P., additional, Wei, A.H., additional, Tiong, I.S., additional, Wall, M., additional, Estey, E., additional, Shaw, C., additional, Exeler, R., additional, Wagenführ, L., additional, Stölzel, F., additional, Thiede, C., additional, Stelljes, M., additional, Lenz, G., additional, Mikesch, J.-H., additional, Serve, H., additional, Ehninger, G., additional, Berdel, W.E., additional, Kramer, M., additional, Krug, U., additional, and Schliemann, C., additional

Published
2019
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24. Friday Leukemiaa Structural Phenomenon.

Author

Rausch, C., Arnreich, C., Rothenberg-Thurley, M., Dufour, A., Schneider, S., Gittinger, H., Bücklein, V., Subklewe, M., Sauerland, C., Görlich, D., Krug, U., Berdel, W. E., Wörmann, B. J., Hiddemann, W., Braess, J., von Bergwelt-Baildon, M., Spiekermann, K., Metzeler, K. H., and Herold, T.

Published
2024
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26. Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia

Author

Krug, U., Berdel, W. E., Gale, R. P., Haferlach, C., Schnittger, S., Mueller-Tidow, C., Braess, J., Spiekermann, K., Staib, P., Beelen, D., Serve, H., Schliemann, C., Stelljes, M., Balleisen, L., Maschmeyer, G., Grueneisen, A., Eimermacher, H., Giagounidis, A., Rasche, H., Hehlmann, R., Lengfelder, E., Thiel, E., Reichle, A., Aul, C., Ludwig, W-D, Kern, W., Haferlach, T., Koepcke, W., Goerlich, D., Sauerland, M. C., Heinecke, A., Woermann, B. J., Hiddemann, W., Buechner, T., Krug, U., Berdel, W. E., Gale, R. P., Haferlach, C., Schnittger, S., Mueller-Tidow, C., Braess, J., Spiekermann, K., Staib, P., Beelen, D., Serve, H., Schliemann, C., Stelljes, M., Balleisen, L., Maschmeyer, G., Grueneisen, A., Eimermacher, H., Giagounidis, A., Rasche, H., Hehlmann, R., Lengfelder, E., Thiel, E., Reichle, A., Aul, C., Ludwig, W-D, Kern, W., Haferlach, T., Koepcke, W., Goerlich, D., Sauerland, M. C., Heinecke, A., Woermann, B. J., Hiddemann, W., and Buechner, T.

Abstract

We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects. 60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts >= 5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P = 0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P = 0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P = 0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes.

Published
2016

27. Patients with acute myeloid leukemia admitted to intensive care units: Scores predicting outcome and post-ICU survival

Author

Pohlen, M., Braess, J., Thudium, J., Schmid, C., Kochanek, M., Kreuzer, K. -A, Goerlich, D., Gerth, U., Rhode, C., Mueller-Tidow, C., Stelljes, M., Buechner, T., Schlimok, G., Hallek, M., Waltenberger, J., Hiddemann, W., Berdel, W. E., Heilmeier, B., Krug, U., Pohlen, M., Braess, J., Thudium, J., Schmid, C., Kochanek, M., Kreuzer, K. -A, Goerlich, D., Gerth, U., Rhode, C., Mueller-Tidow, C., Stelljes, M., Buechner, T., Schlimok, G., Hallek, M., Waltenberger, J., Hiddemann, W., Berdel, W. E., Heilmeier, B., and Krug, U.

Published
2016

28. Ciprofloxacin versus colistin prophylaxis during neutropenia in acute myeloid leukemia: two parallel patient cohorts treated in a single center

Author

Pohlen, M., primary, Marx, J., additional, Mellmann, A., additional, Becker, K., additional, Mesters, R. M., additional, Mikesch, J.-H., additional, Schliemann, C., additional, Lenz, G., additional, Muller-Tidow, C., additional, Buchner, T., additional, Krug, U., additional, Stelljes, M., additional, Karch, H., additional, Peters, G., additional, Gerth, H. U., additional, Gorlich, D., additional, and Berdel, W. E., additional

Published
2016
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29. DNMT3A mutations in exon 23 are associated with improved survival in AML patients treated with Azacytidine plus standard chemotherapy

Author

Tschanter, P., Krug, U., Fueller, M., Klein, M., Goellner, S., Rohde, C., Roellig, C., Thiede, C., Lilly, M. A., Haack, B., Koschmieder, A., Stelljes, M., Dugas, M., Koschmieder, S., Gerss, J., Butterfass-Bahloul, T., Wagner, R., Eveslage, M., Thiem, U., Krause, S. W., Kaiser, U., Kunzmann, V, Steffen, B., Noppeney, R., Herr, W., Baldus, C. D., Schmitz, N., Goetze, K., Reichle, A., Kaufmann, M., Neubauer, A., Schaefer-Eckart, K., Haenel, M., Peceny, R., Frickhofen, N., Kiehl, M., Giagounidis, A., Goerner, M., Repp, R., Link, H., Kiani, A., Naumann, R., Bruemmendorf, T. H., Serve, H., Ehninger, G., Berdel, W. E., Mueller-Tidow, C., Tschanter, P., Krug, U., Fueller, M., Klein, M., Goellner, S., Rohde, C., Roellig, C., Thiede, C., Lilly, M. A., Haack, B., Koschmieder, A., Stelljes, M., Dugas, M., Koschmieder, S., Gerss, J., Butterfass-Bahloul, T., Wagner, R., Eveslage, M., Thiem, U., Krause, S. W., Kaiser, U., Kunzmann, V, Steffen, B., Noppeney, R., Herr, W., Baldus, C. D., Schmitz, N., Goetze, K., Reichle, A., Kaufmann, M., Neubauer, A., Schaefer-Eckart, K., Haenel, M., Peceny, R., Frickhofen, N., Kiehl, M., Giagounidis, A., Goerner, M., Repp, R., Link, H., Kiani, A., Naumann, R., Bruemmendorf, T. H., Serve, H., Ehninger, G., Berdel, W. E., and Mueller-Tidow, C.

Published
2015

30. Mutations of the EPHB6 Receptor Tyrosine Kinase Induce a Pro-Metastatic Phenotype in Non-Small Cell Lung Cancer

Author

Bulk, E.M. (Etmar), Yu, J. (Jun), Hascher, A. (Antje), Koschmieder, S. (Steffen), Wiewrodt, R.G. (Rainer), Krug, U. (Utz), Timmermann, B. (Bernd), Marra, A. (Alessandro), Hillejan, L. (Ludger), Müller-Tidow, C. (Carsten), and Universitäts- und Landesbibliothek Münster

Subjects
Medicine and health, ddc:610
Abstract

Alterations of Eph receptor tyrosine kinases are frequent events in human cancers. Genetic variations of EPHB6 have been described but the functional outcome of these alterations is unknown. The current study was conducted to screen for the occurrence and to identify functional consequences of EPHB6 mutations in non-small cell lung cancer. Here, we sequenced the entire coding region of EPHB6 in 80 non-small cell lung cancer patients and 3 tumor cell lines. Three potentially relevant mutations were identified in primary patient samples of NSCLC patients (3.8%). Two point mutations led to instable proteins. An in frame deletion mutation (del915-917) showed enhanced migration and accelerated wound healing in vitro. Furthermore, the del915-917 mutation increased the metastatic capability of NSCLC cells in an in vivo mouse model. Our results suggest that EPHB6 mutations promote metastasis in a subset of patients with non-small cell lung cancer.

Published
2013

31. Referate

Author

Stich, Walther, Schmidt, D., Hollán, Susanna R., Arlt, H. G., Krug, U., and Eulitz, M.

Published
1971
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36. Comparison Of Different Pretransplant Predictive Scores In Patients With Refractory Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation Including Highdose Melphalan: Results Of a Double-Center Observational Study

Author

Steckel, Nina Kristin, primary, Ditschkowski, Markus, additional, Groth, Christoph, additional, Silling, Gerda, additional, Krug, U., additional, Trenschel, Rudolf, additional, Ottinger, Hellmut, additional, Berdel, Wolfgang E, additional, Koldehoff, Michael, additional, Elmaagacli, Ahmet H., additional, Beelen, Dietrich, additional, and Stelljes, Matthias, additional

Published
2013
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39. Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

Author

Wetzler, M., primary, Mrozek, K., additional, Kohlschmidt, J., additional, Dombret, H., additional, Dohner, H., additional, Pilorge, S., additional, Krug, U., additional, Carroll, A. J., additional, Larson, R. A., additional, Marcucci, G., additional, Hiddemann, W., additional, Buchner, T., additional, and Bloomfield, C. D., additional

Published
2013
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42. Factors Influencing Complete Remission (CR) Rate in Patients ≥ 60 Years with Acute Myeloid Leukemia (AML): Report From the German AML Intergroup Study

Author

Niederwieser, Dietger, primary, Hoffmann, Verena S, additional, Krahl, Rainer, additional, Berdel, Wolfgang E., additional, Sauerland, Maria Cristina, additional, Hiddemann, Wolfgang, additional, Hegenbart, Ute, additional, Woermann, Bernhard Josef, additional, Krug, U., additional, Pönisch, Wolfram, additional, Vucinic, Vladan, additional, Hebenstreit, Karin, additional, Cross, Michael, additional, Niederwieser, Christian, additional, Pfirrmann, Markus, additional, Schulze, A, additional, Kraemer, Alwin, additional, Maschmeyer, Georg, additional, Freund, Mathias, additional, Scholl, S, additional, Heinicke, Thomas, additional, Haehling, D, additional, Wolf, Hans-Heinrich, additional, and Büchner, Thomas, additional

Published
2012
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49. A randomized phase III study of elacytarabine versus limited investigator’s choice in patients with refractory acute myeloid leukemia (AML).

Author

Rizzieri, D., primary, Vey, N., additional, Gobbi, M., additional, Selleslag, D. L. D., additional, Dennis, M. W., additional, Kuliczkowski, K., additional, Krug, U., additional, Moscardo, F., additional, Bron, D., additional, Moicean, A. D., additional, Venditti, A., additional, Jacobsen, T. F., additional, Foss, O., additional, and Giles, F. J., additional

Published
2011
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