Acute Myeloid Leukemia MRD team, drug resistance team and Chronic Myeloid Leukemia team.

Our work is dedicated to improving diagnostics, treatment strategies and ultimately outcome of acute leukemia patients. We focus on detecting residual leukemia cells that remain after chemotherapy: measurable residual disease (MRD). MRD is the major cause of relapse and provides a robust prognostic factor of relapse in acute myeloid leukemia (AML). MRD is used to monitor disease after therapy and assess early signs of recurring leukemia in individual patients, which can be used to guide personalized therapy.

Jacqueline Cloos

The MRD team puts efforts in improving, standardizing and harmonizing MRD assessment by flow cytometry. Based on these efforts, we are central laboratory for MRD assessment in large international clinical trials. In addition, implementation of MRD as an early clinical endpoint are continuous subjects of research by this team of research technicians and PhD students in close collaboration with the clinic (Dr. Dave de Leeuw and Prof dr. Arjan van de Loosdrecht). The team makes significant contributions to the national and international MRD working parties such as the NvC, Dutch AML-MRD working party and ELN. Jacqueline is vice-chair of the ELN-DAVID AML-MRD working party (https://eln-david.org/). Besides publications from in high impact scientific journals, work from the group is reflected in past and recent recommendations on MRD assessment of the ELN that were published in Blood.

MRD assessments may be hampered by the intra-tumor heterogeneity of AML, The role of leukemic stem cells and concurrent clonal evolution during therapy are also research topics that are supervised by Dr.ir. Costa Bachas, senior scientist of the group.

MRD cells remaining after high dose chemotherapy are by definition drug resistant. With the aim to target MRD and reduce the risk of relapse for the individual patient, novel treatment strategies and their potential resistance mechanisms are also studied in collaboration with Dr. G. Jansen. Current examples of drug resistance research are proteasome inhibitors, splicing modulators and cannabidiol.

Besides acute leukemia, we participate in large international clinical trials (PI: dr. Jeroen J.W.M. Janssen, RadboudUMC) for chronic myeloid leukemia (CML) that were designed to investigate which patients were eligible to stop treatment with tyrosine kinase inhibitors. As add-on to these trials, we aim to identify biomarkers to assess if patients can stop treatment successfully. In addition, we investigate the possibility to identify early signs of recurrence of disease.

Group members

Members of the MRD team
  • Costa Bachas, PhD | senior scientist
  • Jesse Tettero, PhD | Visiting fellow
  • Tim Mocking, MSc | PhD-student
  • Tom Reuvekamp, MD, BSc | PhD-student
  • Lukas Haaksma, MD, MSc | PhD-student
  • Kasper Croese, MD, MSc | PhD-student
  • Lok Lam Ngai, MD, MSc | PhD-student (finalizing thesis)
  • Jonathan Go, MSc | Data manager (COHERENT)
  • Angele Kelder, BSc | Chief Technician, Team Coordinator
  • Willemijn Scholten, BSc | Senior Technician,
    Vice-coordinator
  • Yvonne van Oussoren-Brockhoff, BSc | Quality officer of the team
  • Dennis Veldhuizen, BSc | Database developer and maintenance
  • Maaike Heidinga, BSc | Research Technician
  • Mona Fayed, BSc | Research Technician
  • Zohra Rachid, BSc | Research Technician
  • Daphne den Hartog, BSc | Research Technician
  • Laura Oudshoorn, BSc | Research Technician
  • Sven de Regt, BSc | Research Technician
  • Jannemieke Carbaat-Ham, BSc | Research Technician
  • Malika Lechkar, BSc | Research Technician
  • Glenn Franssen, BSc | Research Technician
  • Andie Sullivan, BSc | Research Technician (RESOLVE)
Drug resistance team
  • Nils Evander, MD, MSc | PhD-student
  • Margot Roeten, MD, MSc | PhD-student (finalizing thesis)
  • Johan van Meerloo, MSc | Senior technician
  • Zinia Kwidama, BSc | Senior technician
Members of CML team
  • Pakize Ak, MSc | PhD-student
  • Jim Crama, BSc | Research Technician
  • Bo Kuijk, BSc | Research Technician
  • Feng Groothuizen, BSc | Research Technician
  • Elena Blokker, BSc | Research Technician

Current large consortia projects:

  • COHERENT- Correct diagnosis of hematological cancers for right treatment decisions. KWF-2021infra #13650
    (External) coordinator: Bert van der Reijden, RadboudUMC
  • RESOLVE- Residual disease assessment in hematologic malignancies to improve patient-relevant outcomes across Europe. HORIZON-MISS-2023-CANCER-01-03
    (External) coordinator: Michael Heuser, MHH, Germany
  • MIRACLE - Integrated multi-angle research and training network to eradicate leukemia minimal residual disease. HORIZON-MSCA-2023-DN-01
    (External) coordinator: Linda Smit, Amsterdam UMC

Key publications

Impact of hemodilution on flow cytometry based measurable residual disease assessment in acute myeloid leukemiaJesse M. Tettero, Maaike E. Heidinga, Tim R. Mocking, Glenn Fransen, Angèle Kelder, Willemijn J. Scholten, Alexander N. Snel, Lok Lam Ngai, Costa Bachas, Arjan A. van de Loosdrecht, Gert J. Ossenkoppele, David C. de Leeuw, Jacqueline Cloos, Jeroen J. W. M. Janssen. Leukemia. 2024; 38(3): 630–639.

Prognostic Significance of Measurable Residual Disease Detection by Flow Cytometry in Autologous Stem Cell Apheresis Products in AMLJesse M. Tettero, Yara Buisman, Lok Lam Ngai, Costa Bachas, Bjorn T. Gjertsen, Angèle Kelder, Arjan A. van de Loosdrecht, Markus G. Manz, Thomas Pabst, Willemijn Scholten, Gert J. Ossenkoppele, Jacqueline Cloos, David C. de Leeuw. Hemasphere. 2023 Dec; 7(12): e981.

Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survivalJesse M. Tettero, Lok Lam Ngai, Costa Bachas, Dimitri A. Breems, Thomas Fischer, Bjorn T. Gjertsen, Patrycja Gradowska, Laimonas Griskevicius, Jeroen J.W.M. Janssen, Gunnar Juliusson, Johan Maertens, Markus G. Manz, Thomas Pabst, Jakob Passweg, Kimmo Porkka, Peter J.M. Valk, Bob Löwenberg, Gert J. Ossenkoppele, Jacqueline Cloos Haematologica. 2023 Oct 1; 108(10): 2794–2798.

Prospective validation of the prognostic relevance of CD34+CD38–AML stem cell frequency in the HOVON-SAKK132 trialLok Lam Ngai, Diana Hanekamp, Fleur Janssen, Jannemieke Carbaat-Ham, Maaike A. M. A. Hofland, Mona M. H. E Fayed, Angèle Kelder, Laura Oudshoorn-van Marsbergen, Willemijn J. Scholten, Alexander N. Snel, Costa Bachas, Jesse M. Tettero, Dimitri A. Breems, Thomas Fischer, Bjørn T. Gjertsen, Laimonas Griškevičius, Gunnar Juliusson, Arjan A. van de Loosdrecht, Johan A. Maertens, Markus G. Manz, Thomas Pabst, Jakob R. Passweg, Kimmo Porkka, Peter J. M. Valk, Patrycja Gradowska, Bob Löwenberg, David C. de Leeuw, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Jacqueline Cloos. Blood. 2023 May 25; 141(21): 2657–2661.

Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party Jesse M. Tettero, Sylvie Freeman, Veit Buecklein, Adriano Venditti, Luca Maurillo, Wolfgang Kern, Roland B. Walter, Brent L. Wood, Christophe Roumier, Jan Philippé, Barbara Denys, Jeffrey L. Jorgensen, Marie C. Bene, Francis Lacombe, Adriana Plesa, Monica L. Guzman, Agnieszka Wierzbowska, Anna Czyz, Lok Lam Ngai, Adrian Schwarzer, Costa Bachas, Jacqueline Cloos, Marion Subklewe, Michaela Fuering-Buske, Francesco Buccisano. Hemasphere. 2022 Jan; 6(1): e676.

2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working PartyMichael Heuser, Sylvie D. Freeman, Gert J. Ossenkoppele, Francesco Buccisano, Christopher S. Hourigan, Lok Lam Ngai, Jesse M. Tettero, Costa Bachas, Constance Baer, Marie-Christine Béné, Veit Bücklein, Anna Czyz, Barbara Denys, Richard Dillon, Michaela Feuring-Buske, Monica L. Guzman, Torsten Haferlach, Lina Han, Julia K. Herzig, Jeffrey L. Jorgensen, Wolfgang Kern, Marina Y. Konopleva, Francis Lacombe, Marta Libura, Agata Majchrzak, Luca Maurillo, Yishai Ofran, Jan Philippe, Adriana Plesa, Claude Preudhomme, Farhad Ravandi, Christophe Roumier, Marion Subklewe, Felicitas Thol, Arjan A. van de Loosdrecht, Bert A. van der Reijden, Adriano Venditti, Agnieszka Wierzbowska, Peter J. M. Valk, Brent L. Wood, Roland B. Walter, Christian Thiede, Konstanze Döhner, Gail J. Roboz, Jacqueline Cloos. Blood. 2021 Dec 30; 138(26): 2753–2767.

Splicing factor gene mutations in acute myeloid leukemia offer additive value if incorporated in current risk classificationInge van der Werf, Anna Wojtuszkiewicz, Manja Meggendorfer, Stephan Hutter, Constance Baer, Martijn Heymans, Peter J. M. Valk, Wolfgang Kern, Claudia Haferlach, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Jacqueline Cloos, Torsten Haferlach. Blood Adv. 2021 Sep 14; 5(17): 3254–3265.

Contact

Email: j.cloos@amsterdamumc.nl
Phonenumber: 020 443838

Keywords

Acute Myeloid Leukemia | Measurable Residual Disease | Prognostication | Leukemia Initiating Cells | Drug Resistance | Flow Cytometry