Duque Laboratory

Acute leukemias and allogeneic stem cell transplantation

Scientific focus

The work of our group is focused on the study of molecular pathomechanisms in acute leukemias and on translational studies in allogeneic hematopoietic cell transplantation.

Although the treatment of the acute leukemias has been improved during the last decades, there are still many patients not surviving the disease being relapse and chemotherapy-related complications the main causes of death. Most of survivors are young and therefore very susceptible to the negative long-term effects of chemo- and radiotherapy. In contrast, older patients or patients with comorbidities did not qualify for current intensified therapy regimens being treated with a palliative intention.

We aim to identify novel molecular targets and mechanisms of resistance to small molecules and chemotherapy using novel engineered leukemia mouse models as well as unbiased approaches as shRNA library screen, chromatin immunoprecipitation sequencing and global transcriptome analysis. We employ defined genetic models as the chimeric fusion proteins E2A-PBX1 in acute lymphoblastic leukemias and AML1-ETO in acute myeloid leukemia. Our long-term goal is to develop novel and more rational therapeutic approaches to contribute to the improvement of survival and quality of life of patients

A second major research focus of my group is the identification of molecular markers and clinical parameters including microbiome composition to assess risk for GvHD and relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and for non-relapse mortality after autologous hematopoietic cell transplantation (auto-HCT). Although allo-HCT and auto-HCT are effective curative treatment options for several neoplastic and non-neoplastic diseases, these procedures are not devoid of complications.

Relapse of the underlying disease and Graft-versus-Host Disease (GvHD) are frequent complications after allo-HCT, they contribute to morbidity and mortality and are the main cause of treatment failure. We aim to establish a non-invasive monitoring of circulating nucleic acids and to identify clinical parameters for early detection of relapse and/or GvHD in patients undergoing allo-HCT.

In addition, we are also investigating clinical factors, which contributes to non-relapse mortality in patients undergoing allo-HCT and auto-HCT, focusing especially on the pulmonary function. Our long term goal is to establish a disease risk predictive model, which will lead to preventive or anticipatory therapeutic interventions and improved outcomes of patients after allo-HCT and auto-HCT.

Team

Group leader

Prof. Dr. Jesús Duque-Afonso
Hematologist/Oncologist

jesus.duque.afonso@uniklinik-freiburg.de

Maria Yago Baenas
MD student
maria.yago.baenas@uniklinik-freiburg.de

Ariane Görgen
MD Student
ariane.goergen@uniklinik-freiburg.de

Heike Herzog
Medical Technical Assistant (MTA)
heike.herzog@uniklinik-freiburg.de

Sonja Jickeli
MD Student
sonja.jickeli@uniklinik-freiburg.de

Kristin Walther
MD Student
kristin.walther@uniklinik-freiburg.de

Thilo Thanscheidt
MD Student
thilo.thanscheidt@uniklinik-freiburg.de

Paraschiva Pitu
MD Student
paraschiva.pitu@uniklinik-freiburg.de

Mira Kusterer
MD Student
mira.kusterer@uniklinik-freiburg.de

Ernesto Olcina Aguado
MD Student
ernesto.olcina.aguado@uniklinik-freiburg.de

Radu-Florian Gherman
radu.florian.gherman@uniklinik-freiburg.de

Rebecca Berger
MD Student

rebecca.berger@uniklinik-freiburg.de

Alumni

Dr. rer. nat. Miguel Waterhouse

Dr. med. Gila Mostufi-Zadeh-Haghighi

M. Sc. Alexandra Brand

cand med. Miriam Eckert

Sophie Ewald, MD

Patricia Grüninger, MD

Johana Norona, PhD

Sandra Pennisi, PhD

Projects

Development of artificial intelligence-driven tools based on cytomorphological analysis for diagnostic and outcome prediction of patients with hematological diseases

Collaboration with the CRIION Institute and the Mertelsmann Foundation

Characterization of oncogenic signaling pathways involved in pathogenesis and drug resistance in pre-B cell acute lymphoblastic leukemia (pre-B ALL)

Collaboration with Prof. Dr. M. Cleary and Prof. Dr. M. Bassik (Stanford University, CA, USA)

Genomics-based tools for personalized treatment to reduce chemotherapy burden in pediatric cancer (GEPARD)

Collaboration with Prof. Dr. O. Lohi (University of Tampere, Finland), Prof. Dr. M. Heinäniemi (University of Eastern Finland, Finland), Prof. Dr. V. Wirta (Karolinska Institutet, Sweden) and Prof. Dr. J. Hauer, (University of Dresden, Germany)

Identification of factors for GvHD and relapse risk assessment after allogeneic hematopoietic cell transplantation

Collaboration with Prof. Dr. J. Finke (University of Freiburg, Germany).

Understanding transcriptional regulation by chromatin-modifying enzymes in acute myeloid leukemia (AML)

Collaboration with Prof. Dr. Michael Lübbert (University of Freiburg, Germany)

Further Information

Funding

05/2025-04/2028 Research Grant from the EP PerMed co-founded by die European Commission for the project “Genomics- and biomarkers-based tools for personalized treatment to reduce chemotherapy burden in pediatric leukemia (GEPARD-2) ” (36 Monate) (01KU2515) .

07/2024 – 06/2027 Research grant from the Mertelsmann Foundation for the project “Development of artificial intelligence-driven tools based on cytomorphological analysis for diagnostic and outcome prediction of patients with acute hematological Diseases.

01/2020 - 12/2022 Research Grant from the German Research Foundation (DFG) for the project “Mechanisms of resistance to targeted therapy and chemotherapy in acute lymphoblastic leukemias”.

07/2019 - 06/2022 Research Grant from the ERA PerMed cofounded by the European Commission for the project “Genomics-based tools for personalized treatment to reduce chemotherapy burden in pediatric cancer (GEPARD)”.

01/2019 - 12/2020 Research Grant from Else Kröner-Fresenius-Stiftung for the project “Non-invasive monitoring of minimal residual disease and Graft-versus-Host Disease by circulating nucleic acids after allogeneic hematopoietic transplantation”.

01/2017 - 12/2017 Research Grant from the Research Committee (Forschungskommission) of the University of Freiburg for the project “Functional characterization of the TGFβ signalling pathway in acute lymphoblastic leukemia”.

Cooperations

Internal collaborations

Dr. M. Kalweit, University of Freiburg Medical Center
Prof. Dr. J. Finke, University of Freiburg Medical Center
Prof. Dr. M. Lübbert, University of Freiburg Medical Center
Prof. Dr. R. Zeiser, University of Freiburg Medical Center
Prof. Dr. M. Engelhardt, University of Freiburg Medical Center
PD Dr. R. Marks, University of Freiburg Medical Center
Dr. C. Miething, University of Freiburg Medical Center
PD Dr. R Sankowski, Neuropathology, University of Freiburg Medical Center
Prof. Dr. B. Bengsch, Gastroenterology, University of Freiburg Medical Center
Prof. Dr. O. Groß, Neuropathology, University of Freiburg Medical Center
PD Dr. P. Bronsert, Pathology, University of Freiburg Medical Center
Prof. Dr. T. Hartmann, Hematology/Oncology, University of Freiburg Medical Center
Prof. Dr. O. Schilling, Pathology, University of Freiburg Medical Center
PD Dr. F. Scherer, Dept. of Hematology/Oncology, University of Freiburg Medical Center

External collaborations

Dr. F. Auer, TU Munich, Germany
Prof. Dr. J. Nordlund, Uppsala University, Sweden.
Prof. Dr. M. Cleary, Stanford University, CA , USA
Prof. Dr. M. Bassik, Stanford University, CA, USA
Prof. Dr. O. Lohi, University of Tampere and Tampere University Hospital, Finland
Prof. Dr. M. Heinäniemi, University of Eastern Finland, Finland
Prof. Dr. V. Wirta, Karolinska Institutet, Sweden
Prof. Dr. J. Hauer, TU Munich, Germany
Prof. Dr. A. Borkhardt, University of Düsseldorf, Germany
Prof. Dr. G. Cario, University Medical Center Schleswig-Holstein (Kiel), Germany
Prof. Dr. M. Schrappe, University Medical Center Schleswig-Holstein (Kiel), Germany
Dr. Lennart Lenk, University of Kiel
LABMaiTE, Freiburg.

Graphic design

C. Duque-Afonso, PhD, University of Göttingen, Germany

Publications

Top publications

Kusterer M, Lahnalampi M, Voutilainen M, Brand A, Pennisi S, Norona J, Gentile G, Herzog H, Greve G, Lübbert M, Sipola M, Kaartinen E, Sankowski R, Prinz M, Killmer S, Lago MS, Bengsch B, Cysar SR, Aumann K, Werner M, Duyster J, Lohi O, Heinäniemi M, Duque-Afonso J. (2025) Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure. Hemasphere. Feb 3;9(2):e70071.
Gentile G, Poggio T, Catalano A, Voutilainen M, Lahnalampi M, Andrade-Martinez M, Ma T, Sankowski R, Goncharenko L, Tholen S, Han K, Morgens DW, Prinz M, Lübbert M, Engel S, Hartmann TN, Cario G, Schrappe M, Lenk L, Stanulla M, Duyster J, Bronsert P, Bassik M, Cleary ML, Schilling O, Heinäniemi M, Duque-Afonso J. (2024) Development of combination therapies with BTK inhibitors and dasatinib to treat CNS-infiltrating E2A-PBX1+/preBCR+ ALL. Blood Adv. Apr 10:bloodadvances.2023011582.
Duque-Afonso J, Veratti P, Rehman UU, Herzog H, Mitschke J, Greve G, Eble J, Berberich B, Thomas J, Pantic M, Waterhouse M, Gentile G, Heidenreich O, Miething C, Lübbert M. (2024) Identification of epigenetic modifiers essential for growth and survival of AML1/ETO-positive leukemia. Int J Cancer. Dec 1;155(11):2068-2079. doi: 10.1002/ijc.35134.
Gherman RF, Ewald S, Ihorst G, Strüßmann T, Zeiser R, Wäsch R, Bertz H, Stolz D, Duyster J, Finke J, Marks R, Engelhardt M, Duque-Afonso J. (2023) Identification of clinical factors impacting outcome in patients undergoing autologous hematopoietic cell transplantation after BEAM and TEAM conditioning. Eur J Haematol.;. doi: 10.1111/ejh.14118
Functional Characterization of Transforming Growth Factor- Signaling in Dasatinib Resistance and Pre-BCR+ Acute Lymphoblastic Leukemia.
Mostufi-Zadeh-Haghighi G, Veratti P, Zodel K, Greve G, Waterhouse M, Zeiser R, Cleary ML, Lübbert M and Duque-Afonso J.
Cancers 2023, 15(17), 4328; https://doi.org/10.3390/cancers15174328
Monitoring of Measurable Residual Disease Using Circulating DNA after Allogeneic Hematopoietic Cell Transplantation.
Waterhouse M, Pennisi S, Pfeifer D, Scherer F, Zeiser R, Duyster J, Bertz H, Finke J, Duque-Afonso J.
Cancers (Basel). 2022 Jul 7;14(14):3307. https://doi.org/10.3390/cancers14143307.
Functional characterization of the PI3K/AKT/MTOR signaling pathway for targeted therapy in B-precursor acute lymphoblastic leukemia.
Grüninger PK, Uhl F, Herzog H, Gentile G, Andrade-Martinez M, Schmidt T, Han K, Morgens DW, Bassik MC, Cleary ML, Gorka O, Zeiser R, Groß O, Duque-Afonso J.
Cancer Gene Ther. 2022 Nov;29(11):1751-1760. doi: 10.1038/s41417-022-00491-0
Comparison of fludarabine-melphalan and fludarabine-treosulfan as conditioning prior to allogeneic hematopoietic cell transplantation-a registry study on behalf of the EBMT Acute Leukemia Working Party.
Duque-Afonso J, Finke J, Labopin M, Craddock C, Protheroe R, Kottaridis P, Tholouli E, Byrne JL, Orchard K, Salmenniemi U, Hilgendorf I, Hunter H, Nicholson E, Bloor A, Snowden JA, Verbeek M, Clark A, Savani BN, Spyridonidis A, Nagler A, Mohty M.
Bone Marrow Transplant. 2022 Aug;57(8):1269-1276. doi: 10.1038/s41409-022-01646-1
The impact of pulmonary function in patients undergoing autologous stem cell transplantation.
Duque-Afonso J, Ewald S, Ihorst G, Waterhouse M, Struessmann T, Zeiser R, Wäsch R, Bertz H, Müller-Quernheim J, Duyster J, Finke J, Marks R, Engelhardt M.
Blood Adv. 2021 Nov 9;5(21):4327-4337. doi: 10.1182/bloodadvances.2021004863
Colon and liver tissue damage detection using methylated SESN3 and PTK2B genes in circulating cell-free DNA in patients with acute graft-versus-host disease.
Waterhouse M, Pennisi S, Pfeifer D, Deuter M, von Bubnoff N, Scherer F, Strüssmann T, Wehr C, Duyster J, Bertz H, Finke J, Duque-Afonso J.
Bone Marrow Transplant. 2021 Feb;56(2):327-333. doi: 10.1038/s41409-020-01090-z
Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation.
Duque-Afonso J, Ihorst G, Waterhouse M, Zeiser R, Wäsch R, Bertz H, Yücel M, Köhler T, Müller-Quernheim J, Marks R, Finke J.
Bone Marrow Transplant. 2021 Jan; 56(1):110-120. doi: 10.1038/s41409-020-0986-2
Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation.
Waterhouse M, Pfeifer D, Duque-Afonso J, Follo M, Duyster J, Depner M, Bertz H, Finke J.
Clin Chem Lab Med. 2019 57(5):641-647. doi: 10.1515/cclm-2018-0827.
Cell-free DNA characteristics and chimerism analysis in patients after allogeneic cell transplantation.
Duque-Afonso J, Waterhouse M, Pfeifer D, Follo M, Duyster J, Bertz H, Finke J.
Clin Biochem. 2018; 52:137-141. doi: 10.1016/j.clinbiochem.2017.11.015.
CBP Modulates Sensitivity to Dasatinib in Pre-BCR⁺ Acute Lymphoblastic Leukemia.
Duque-Afonso J, Lin CH, Han K, Morgens DW, Jeng EE, Weng Z, Jeong J, Wong SHK, Zhu L, Wei MC, Chae HD, Schrappe M, Cario G, Duyster J, Xiao X, Sakamoto KM, Bassik MC, Cleary ML.
Cancer Res. 2018; 78(22):6497-6508. doi: 10.1158/0008-5472.CAN-18-1703