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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Lübbert Laboratory

Cancer Epigenetics

Scientific focus

Our long-term goal is a better understanding of the genetic and epigenetic pathomechanisms leading to leukemia and other cancers, as a basis for the development of chemotherapy-free treatment approaches.

Our research activities include mechanistic studies of epigenetic gene silencing (resulting in tumor suppressor inactivation, arrested differentiation, and immune evasion), and the development of preclinical models to reactivate these silenced genes. Validation of these approaches includes correlative studies within clinical trials of  DNA-hypomethylating drugs and other chromatin-modifying agents in acute myeloid leukemia (AML), in order to identify novel biomarkers predicting response to epigenetically active drugs (epi-drugs), and to better understand the genetic and epigenetic mechanisms of resistance to these therapies. Experimental techniques used in the lab include culturing of AML and lung cancer cells, and purification of primary leukemia blood blasts from patients receiving epi-drug therapies. Molecular biology techniques: DNA methylome analyses, RNA-seq, ATAC-seq, ChIP-seq etc.

In order to more rapidly advance this "bench-to-bedside - and back" approach within a larger network of investigators, we have established collaborations with numerous other groups, e.g. via preclinical and correlative studies on DNA-demethylating therapy and LSD1 inhibition in AML and MDS. Similarly, we have initiated a DFG Research Consortium on epigenetics and aging in AML: Forschungsgruppe 2674, funded since 2017, Coordinators: M. Lübbert, C. Plass. We also participate in the DFG CRC 992 (Medep) since its inception in 2012. In order to advance epigenetically-based therapies in the clinic, we are coordinating several national and European investigator-initiated clinical trials, e.g. within the EORTC Leukemia Cooperative Group.

Team

Principal Investigator
Bettina Berberich

Bettina Berberich
M.Sc., cand. med. (research assistant)
bettina.berberich@uniklinik-freiburg.de

Dennis Zimmer
M.Sc. (scientific associate)

dennis.zimmer@uniklinik-freiburg.de

Usama Ur Rehman
M.Sc. (PhD student)

usama-ur.rehman@uniklinik-freiburg.de

Helena Bresser
cand. med. (MD thesis student)

helena.bresser@uniklinik-freiburg.de

Kevin Moschallski
cand. med. (MD thesis student)

kevin.moschallski@uniklinik-freiburg.de

Ruth Meier

Ruth Meier
physician (MD thesis student)
ruth.meier@uniklinik-freiburg.de

Victor Ruf
(technician apprentice)

victor.ruf@uniklinik-freiburg.de

Tobias Ma

Tobias Ma
M.Sc. (technician)
tobias.ma@uniklinik-freiburg.de

Clinician-Scientists

Julia Stomper, MD (2017 – 2020)

Tina Jöckel, MD (2010 – 2012)

Jesús Duque-Afonso, MD (2010 – 2012)

Barbara Deschler, MD (2003 – 2011)

Nina Chevalier, MD (2008 – 2011)

Heiko Becker, MD (2005 – 2008)

Tobias Berg, MD (2002 – 2008)

Peter Haas, MD (2001 – 2008)

Björn Rüter, MD (2001 – 2007)

Rainer Claus, MD (1999 – 2006)

Björn Hackanson, MD (2003 – 2005)

Claudia Müller-Schmah, MD (2001 – 2004)

Michael Daskalakis, MD (1998 – 2001)

Jens Würthner, MD (1996 – 1998)

Daniel Jonas, MD (1989 – 1991)


Postdocs

Gabriele Greve, PhD (2017 – 2021)

John Rotondo, PhD (2017 – 2018)

Nadja Blagitko-Dorfs, PhD (2007 – 2016)

Margit Sauer, PhD (2012 – 2014)

Roland  Weis, MD (2007 – 2011)

Manfred Fliegauf, PhD (2008 – 2010)

Bernhard Kleine, PhD (2006 – 2008)


Statistician

Ljudmila Bogatyreva (2007 – 2017)


PhD students

Tzu-Ting Wei (2018 – 2019)

Zoe Sawitzki (2016 – 2018)

Gabriele Greve (2010 – 2017)

Pascal Schlosser (2012 – 2016)

Gregor Klaus (2011 – 2015)

Yi Jiang (2005 – 2007)

Manfred Fliegauf (1996 – 2002)


Medical doctoral students

Kai Rejeski (2015 – 2019)

Insa Schiffmann (2013 – 2017)

Aitomi Essig (2010 – 2012)

Jan Kay Hiller (2008 – 2011)

David Leander Rimmele (2008 – 2010)

Maria Leticia Solari (2007 – 2011)

Jesús Duque-Afonso (2004 – 2010)

Maika Almstedt (2004 – 2009)

Lena Kasten (2004 - 2007)

Yalin Guo (2001 – 2004)

Rainer Claus (1999 – 2004)

Carsten Kobe (1998 – 2000)

Anna Peuckert (1998 – 2000)

Claudia Pötzsch (1995 – 1997)

Arndt Schottelius (1991 – 1994)


Thesis students

Annika Heck, B.Sc. (2020)

Anne Rubarth, M.Sc. (2018 – 2020)

Kay Chmielewski, M.Sc. (2017 – 2018)

Akinnurun Oluwafemi, B.Sc. (2015)

Thomas Benkler (2009)

Sara Cohen (2008 – 2009)

Maike Buchner, M.Sc. (2005 – 2006)

Josephus Kim (2005-2006)


Technicians

Ruhtraut Ziegler (2014 – 2021)

Frederik Henes (2018 – 2021)

Carmen Strittmatter (2014 – 2016)

Angela Koch (1994 – 2010)

Brigitte Joos (2007 – 2008)

Melanie Feuerstein (2005 – 2006)

Mahmoud Abdelkarim (2001 – 2005)

Johanna Römmelt (1991 – 1996)

Regina Ruszcinsky (1990 – 1992)


Student Research Assistants

Dana Eble, B. Sc. (2018)

Sina Bengel, M.Sc. (2016 – 2018)

Philipp N. Sander, M.Sc. (2014 – 2018)

Tina Röder, M.Sc. (2016 – 2018)

Juliane Steinmann (2012 – 2016)

Katharina Düker, M.Sc. (2014 – 2016)

Sandra Nitsch, M.Sc. (2014 – 2015)

Julian Eble, M.Sc. (2014 – 2015)

Monique Braun (2008 – 2011)

Maren Prinz (2008 – 2010)

Tobias Berg (2002 – 2005)

Peter Haas (2002 – 2006)

May, 2021

Review published

Hypomethylating agents (HMA) for the treatment of acute myeloid leukemia and myelodysplastic syndromes: mechanisms of resistance and novel HMA-based therapies.
Stomper J, Rotondo JC, Greve G, Lübbert M. Leukemia. 2021 May 6. doi: 10.1038/s41375-021-01218-0. Online ahead of print. PMID: 33958699

 

May, 2021

Second funding period for DFG FOR2674 grant accepted

Titel: Alters-assoziierte epigenetische Veränderungen als therapeutischer Ansatzpunkt in der Behandlung der akuten myeloischen Leukämie,
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 336840530

 

April, 2021

Original Article published

Integrative study of EZH2 mutational status, copy number, protein expression and H3K27 trimethylation in AML/MDS patients.
Stomper J, Meier R, Ma T, Pfeifer D, Ihorst G, Blagitko-Dorfs N, Greve G, Zimmer D, Platzbecker U, Hagemeijer A, Schmitt-Graeff I, Lübbert M.
Clin Epigenetics. 2021 Apr 12;13(1):77.
doi: 10.1186/s13148-021-01052-2. PMID: 33845873

DECIDER-1

„Prospective Randomized Multicenter Phase II Trial of Low-dose Decitabine (DAC) Administered Alone or in Combination With the Histone Deacetylase Inhibitor Valproic Acid (VPA) and All-trans Retinoic Acid (ATRA) in Patients > 60 Years With Acute Myeloid Leukemia Who Are Ineligible for Induction Chemotherapy“
(NCT00867672, AMLSG 14-09)

Phase II, recruitment period: 2011 – 2016

204 recruited participants

 

EORTC AML21 („inDACtion vs. induction“)

„10-day Decitabine Versus Conventional Chemotherapy ("3+7") Followed by Allografting in AML Patients ≥ 60 Years: a Randomized Phase III Study of the EORTC Leukemia Group, CELG, GIMEMA and German MDS Study Group (NCT02172872, EORTC 1301)

Phase III, recruitment period: 2015 – 2019

606 recruited participants

 

TRANSATRA

„Phase I/II Study of Sensitization of Non-M3 Acute Myeloid Leukemia (AML) Blasts to All-trans Retinoic Acid (ATRA) by Epigenetic Treatment With Tranylcypromine (TCP), an Inhibitor of the Histone Lysine Demethylase 1 (LSD1)“ (NCT02717884)

Phase I/II, recruitment period: 2015 – 2020

25 recruited participants

 

EORTC 06011

„Intravenous Low-Dose Decitabine Versus Supportive Care in Elderly Patients With Primary Myelodysplastic Syndrome (MDS) (>10% Blasts or High-Risk Cytogenetics), Secondary MDS or Chronic Myelomonocytic Leukemia (CMML) Who Are Not Eligible for Intensive Therapy:
An EORTC-German MDS Study Group Randomized Phase III Study“ (NCT00043134)

Phase III, recruitment period: 2003 – 2007

233 recruited participants

 

FR00331

„A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy“
(DRKS00000069)

Phase II, recruitment period: 2003 – 2007

227 recruited participants

 

DECIDER-2

„Prospective randomized multicenter phase III trial of decitabine and Venetoclax administered in combination with all-trans retinoic acid or placebo in patients with acute myeloid leukemia who are ineligible for induction chemotherapy“ (AMLSG 32-21)

Phase III, to be initiated, recruitment start projected for QIV 2021, planned: 250 participants

  • Maya André, MD PhD, Tübingen
  • Geoffroy Andrieux, PhD, Freiburg
  • Heiko Becker, MD, Freiburg
  • Markus Bender, PhD, Würzburg
  • Tobias Berg, MD, Hamilton, Canada
  • Melanie Börries, MD PhD, Freiburg
  • Steffen Böttcher, MD, Zürich
  • Benedikt Brors, PhD, DKFZ Heidelberg
  • Gesine Bug, MD, Frankfurt
  • Nina Cabezas-Wallscheid, PhD, MPI-IE Freiburg
  • Michael Cleary, MD, Stanford University, CA
  • Sven Diederichs, PhD, Freiburg
  • Hartmut Döhner, MD, Ulm
  • Konstanze Döhner, MD, Ulm
  • Jesús Duque-Afonso, MD, Freiburg
  • Jürgen Finke, MD, Freiburg
  • Christian Flotho, MD, Freiburg
  • Arnold Ganser, MD, Hannover
  • Ulrich Germing, MD, Düsseldorf
  • Elizabeth Griffiths, MD, Buffalo, NY
  • Björn Hackanson, MD, Augsburg
  • Anne Hagemeijer, PhD, Leuven, Belgium
  • Michael Heuser, MD, Hannover
  • Gerwin Huls, MD, Groningen, The Netherlands
  • Gabriele Ihorst, PhD, ZKS Freiburg
  • Joop Jansen, PhD, Nijmegen, The Netherlands
  • Thomas Jenuwein, PhD, MPI-IE Freiburg
  • Peter A. Jones, PhD, VAI, Grand Rapids, MI
  • Manfred Jung, PhD, Freiburg
  • Michal Kicinski, PhD, EORTC, Brussels, Belgium
  • Mark Kirschbaum, MD, New York, NY
  • Raphael Koch, MD, Göttingen
  • Phillip Koeffler, MD, Los Angeles, CA
  • Daniel Lipka, MD, DKFZ Heidelberg
  • Philipp Mallm, PhD, DKFZ Heidelberg
  • Richard Momparler, PhD, Montréal, Canada
  • Andreas Neubauer, MD, Marburg
  • Seishi Ogawa, MD, Kyoto, Japan
  • Dietmar Pfeifer, PhD, Freiburg
  • Christoph Plass, PhD, DKFZ Heidelberg
  • Uwe Platzbecker, MD, Leipzig
  • Hugh Y. Rienhoff, MD, San Francisco, CA
  • Karsten Rippe, PhD, DKFZ Heidelberg
  • Michael Schmitt, MD, Heidelberg
  • Annette Schmitt-Gräff, MD, Freiburg
  • Claudia Schmoor, PhD, ZKS Freiburg
  • Roland Schüle, PhD, Freiburg
  • Jan Stratmann, MD, Frankfurt
  • Stefan Suciu, PhD, EORTC, Brussels, Belgium
  • Felicitas Thol, MD, Hannover
  • Adriano Venditti, Rome
  • Pierre W. Wijermans, MD PhD, The Hague, The Netherlands
  • Robert Zeiser, MD, Freiburg

Selected preclinical and translational publications (2012 – 2021)

  1. Stomper J, Meier R, Ma T, Pfeifer D, Ihorst G, Blagitko-Dorfs N, Greve G, Zimmer D, Platzbecker U, Hagemeijer A, Schmitt-Graeff A, Lübbert L. Integrative study of EZH2 mutational status, copy number, protein expression and H3K27 trimethylation in AML/MDS patients.
    Clin. Epigenetics 2021
     
  2. Greve G, Schüler J, Grüning BA, Berberich B, Stomper J, Zimmer D, Gutenkunst L, Bönisch U, Meier R, Blagitko-Dorfs N, Grishina O, Pfeifer D, Weichenhan D., Plass C, Lübbert M (2020) Decitabine induces gene derepression on monosomic chromosomes: in vitro and in vivo effects in adverse-risk cytogenetics AML. Cancer Res.  DOI: 10.1158/0008-5472.CAN-20-1430 Published February 2021
     
  3. Niemöller C, Wehrle J, Riba J, Claus R, Renz N, Rhein J, Bleul S, Stosch JM, Duyster J, Plass C, Lutsik P, Lipka DB,  Lübbert M, Becker H.
    Bisulfite-free epigenomics and genomics of single cells analyzed by methylation sensitive restriction (epi-gSCAR). Comm. Biol. 2021
     
  4. Schlosser P, Knaus J, Schmutz M, Dohner K, Plass C, Bullinger L, Claus R, Binder H, Lübbert M, Schumacher M. Netboost: Boosting-supported Network Analysis Improves High-Dimensional Omics Prediction in Acute Myeloid Leukemia and Huntington's Disease.
    IEEE/ACM Trans Comput Biol Bioinform. May 1, 2020. PP
     
  5. Becker H, Pfeifer D, Ihorst G, Pantic M, Wehrle J, Rüter BH, Bullinger L, Hackanson B, Germing U, Kuendgen A, Platzbecker U, Döhner K, Ganser A, Hagemeijer A, Wijermans PW, Döhner H, Duyster J, Lübbert M. Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia. Ann Hematol. 99:1551-1560, 2020
     
  6. Becker H, Greve G, Kataoka K, Mallm JP, Duque-Afonso J, Ma T, Niemöller C, Pantic M, Duyster J, Cleary ML, Schüler J, Rippe K, Ogawa S, Lübbert M. Identification of enhancer of mRNA decapping 4 as a novel fusion partner of MLL in acute myeloid leukemia. Blood Adv. 3;761–765, 2019
     
  7. Barth J, Abou-El-Ardat K, Dalic D, Kurrle N, Maier AM, Mohr S, Schütte J, Vassen L, Greve G, Schulz-Fincke J, Schmitt M, Tosic M, Metzger E, Bug G, Khandanpour C, Wagner SA, Lübbert M, Jung M, Serve H, Schüle R, Berg T. LSD1 inhibition by tranylcypromine derivatives interferes with GFI1-mediated repression of PU.1 target genes and induces differentiation in AML. Leukemia. 33:1411-1426, 2019
     
  8. Blagitko-Dorfs N, Schlosser P, Greve G, Pfeifer D, Meier R, Baude A, Brocks D, Plass C., Lübbert M. Combination Treatment of Acute Myeloid Leukemia Cells with DNMT and HDAC Inhibitors: Predominant Synergistic Gene Downregulation Associated with Gene Body Demethylation.
    Leukemia. 33:945-956, 2019.
     
  9. Lipka DB, Witte T, Toth R, Yang J, Wiesenfarth M, Nöllke P, Fischer A, Brocks D, Gu Z, Park J, Strahm B, Wlodarski M, Yoshimi A, Claus R, Lübbert M, Busch H, Boerries M, Hartmann M, Schönung M, Kilik U, Langstein J, Wierzbinska JA, Pabst C, Garg S, Catalá A, De Moerloose B, Dworzak M, Hasle H, Locatelli F, Masetti R, Schmugge M, Smith O, Stary J, Ussowicz M, van den Heuvel-Eibrink MM, Assenov Y, Schlesner M, Niemeyer C, Flotho C, Plass C. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nat Commun. 8:2126, 2017
     
  10. Brocks D, Schmidt CR, Daskalakis M, Jang HS, Shah NM, Li D, Li J, Zhang B, Hou Y, Laudato S, Lipka DB, Schott J, Bierhoff H, Assenov Y, Helf M, Ressnerova A, Islam MS, Lindroth AM, Haas S, Essers M, Imbusch CD, Brors B, Oehme I, Witt O, Lübbert M, Mallm JP, Rippe K, Will R, Weichenhan D, Stoecklin G, Gerhäuser C, Oakes CC, Wang T, Plass C. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat Genet. 49:1052-1060, 2017.
     
  11. Hiller JK, Schmoor C, Gaidzik VI, Schmidt-Salzmann C, Yalcin A, Abdelkarim M, Blagitko-Dorfs N, Döhner K, Bullinger L, Duyster J, Lübbert M, Hackanson B. Evaluating the impact of genetic and epigenetic aberrations on survival and response in acute myeloid leukemia patients receiving epigenetic therapy. Ann Hematol. 96:559-565, 2017.
     
  12. Lübbert M, Ihorst G, Sander PN, Bogatyreva L, Becker H, Wijermans PW, Suciu S, Bissé E, Claus R. Elevated fetal haemoglobin is a predictor of better outcome in MDS/AML patients receiving 5-aza-2'-deoxycytidine (Decitabine). Br J Haematol. 176:609-617, 2017.
     
  13. Madan V, Shyamsunder P, Han L, Mayakonda A, Nagata Y, Sundaresan J, Kanojia D, Yoshida K, Ganesan S, Hattori N, Fulton N, Tan KT, Alpermann T, Kuo MC, Rostami S, Matthews J, Sanada M, Liu LZ, Shiraishi Y, Miyano S, Chendamarai E, Hou HA, Malnassy G, Ma T, Garg M, Ding LW, Sun QY, Chien W, Ikezoe T, Lill M, Biondi A, Larson RA, Powell BL, Chng WJ, Tien HF, Heuser M, Ganser A, Koren-Michowitz M, Kornblau SM, Kantarjian HM, Nowak D, Hofmann WK, Yang H, Stock W, Ghavamzadeh A, Alimoghaddam K, Haferlach T, Ogawa S, Shih LY, Mathews V, Koeffler HP. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia. Leukemia. 30:1672-81, 2016.
     
  14. Greve G, Schiffmann I, Pfeifer D, Pantic M, Schüler J, Lübbert M. The pan-HDAC inhibitor panobinostat acts as a sensitizer for erlotinib activity in EGFR-mutated and -wildtype non-small cell lung cancer cells. BMC Cancer. 15:947, 2015
     
  15. Greve G, Schiffmann I, Lübbert M. Epigenetic priming of non-small cell lung cancer cell lines to the antiproliferative and differentiating effects of all-trans retinoic acid. J Cancer Res Clin Oncol. 141:2171-80, 2015
     
  16. Becker H, Yoshida K, Blagitko-Dorfs N, Claus R, Pantic M, Abdelkarim M, Niemöller C, Greil C, Hackanson B, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Döhner K, Schnittger S, Henneke P, Niemeyer CM, Flotho C, Pfeifer D, Ogawa S, Lübbert M. Tracing the development of acute myeloid leukemia in CBL-syndrome. Blood. 123:1883-1886, 2014
     
  17. Blagitko-Dorfs N, Jiang Y, Duque-Afonso J, Hiller J, Yalcin A, Greve G, Abdelkarim M, Hackanson B, Lübbert M. Epigenetic Priming of AML Blasts for All-trans Retinoic Acid-Induced Differentiation by the HDAC Class-I Selective Inhibitor Entinostat. PLoS One. 8(10):e75258, 2013
     
  18. Solari L, Bauer T, Dicker F, Haferlach C, Grießhammer M, Schnittger S, Becker H, Lübbert M. A Novel Recurrent AML1-ETO fusion: Tight in vivo Association with BCR-ABL1. Leukemia. 27(6): 1397-400, 2013
     
  19. Claus R, Pfeifer D, Almstedt M, Zucknick M, Hackanson B, Plass C, Lübbert M. Decitabine induces very early in vivo DNA methylation changes in blasts from patients with acute myeloid leukemia. Leuk. Res. 37(2):190-6, 2013
     
  20. Hackanson B, Rimmele L, Benkißer M, Abdelkarim M, Fliegauf M, Jung M, Lübbert M. HDAC6 as a target for antileukemic drugs in acute myeloid leukemia. Leuk. Res. 36(8):1055-62, 2012.

Selected clinical publications (2012 – 2021)

  1. Lübbert M, Grishina O, Schmoor C, Schlenk RF, Jost E, Crysandt M, Heuser M, Thol F, Salih HR, Schittenhelm MM, Germing U, Kuendgen A, Götze KS, Lindemann H-W, Müller-Tidow C, Heil G, Scholl S, Bug G, Schwänen C, Giagounidis A, Neubauer A, Krauter J, Brugger W, de Wit M, Wäsch R, Becker H, May AM, Duyster J, Döhner K, Ganser A, Hackanson B, Döhner H. Valproate and retinoic acid in combination with decitabine in elderly nonfit patients with acute myeloid leukemia: Results of a multicenter, randomized, 2 × 2, phase II trial.. J Clin Oncol. 38:257-270, 2020.
     
  2. Metzelder SK, Schroeder T, Lübbert M, Ditschkowski M, Götze K, Scholl S, Meyer RG, Dreger P, Basara N, Fey MF, Salih HR, Finck A, Pabst T, Giagounidis A, Kobbe G, Wollmer E, Finke J, Neubauer A, Burchert A. Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation. Eur J Cancer. 86:233-239, 2017
     
  3. Schlenk RF, Lübbert M, Benner A, Lamparter A, Krauter J, Herr W, Martin H, Salih HR, Kündgen A, Horst HA, Brossart P, Götze K, Nachbaur D, Wattad M, Köhne CH, Fiedler W, Bentz M, Wulf G, Held G, Hertenstein B, Salwender H, Gaidzik VI, Schlegelberger B, Weber D, Döhner K, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study. Ann Hematol. 95:1931-1942, 2016.
     
  4. Lübbert M, Suciu S, Hagemeijer A, Rüter B, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Muus P, Pflüger KH, Schaefer HE, Bogatyreva L, Aul C, de Witte T, Ganser A, Becker H, Huls G, van der Helm L, Vellenga E, Baron F, Marie JP, Wijermans PW. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: Results of a Subgroup Analysis of the Randomized Phase III Study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group. Ann Hematol. 95:191-9, 2016.
     
  5. Becker H, Suciu S, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Muus P, Pflüger, K-H, Hagemeijer A, Schaefer H-E, Baron F, Ganser A, Aul C, de Witte T, Wijermans PW, Lübbert M. Decitabine vs. Best Supportive Care in Older Patients With Refractory Anaemia With Excess Blasts in Transformation (RAEBt), or Low Blast Count Acute Myeloid Leukaemia (AML) According to World Health Organization Criteria.
    Ann Hematol. 94:2003-13, 2015
     
  6. Steinmann J, Bertz H, Wäsch R, Marks R, Zeiser R, Bogatyreva L, Finke J, Lübbert M. 5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft. Bone Marrow Transplant. 50:690-5, 2015.
     
  7. Döhner H, Lübbert M, Fiedler W, Fouillard L, Haaland A, Brandwein JM, Lepretre S, Reman O, Turlure P, Ottmann OG, Müller-Tidow C, Krämer A, Raffoux E, Döhner K, Schlenk RF, Voss F, Taube T, Fritsch H, Maertens J. Randomized, phase 2 trial comparing low-dose cytarabine with or without volasertib in AML patients not suitable for intensive induction therapy. Blood. 124:1426-33, 2014.
     
  8. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto. German-Austrian Acute Myeloid Leukemia Study Group. Study Alliance Leukemia, Retinoic acid and arsenic trioxide for acute promyelocytic leukemia.
    N. Engl. J. Med. 369:111-21, 2013
     
  9. Lübbert M, Rüter BH, Claus R, Schmoor C, Schmid M,  Germing U, Kuendgen A, Rethwisch V, Ganser A, Platzbecker U, Galm O, Brugger W, Heil G, Hackanson B, Deschler B, Döhner K, Hagemeijer A, Wijermans PW, Döhner H. A multicenter phase II trial of continued Decitabine as first-line treatment of older AML patients judged unfit for induction chemotherapy. Haematologica. 97:393-401, 2012