The work of Jacqueline Cloos is dedicated to improving diagnostics, treatment strategies and ultimately outcome of acute leukemia patients. She focuses on residual leukemia cells that remain after chemotherapy: minimal residual disease (MRD). MRD is the major cause of relapse in cancer and leukemia. MRD is assessed in her research group using flow cytometry and is a robust prognostic factor for relapse risk, guides personalized therapy and important for monitoring disease to assess early signs of recurring leukemia in individual patients. Improvements on MRD and implementation of MRD as an early clinical endpoint are continuous subjects of research by a team of 10 research technicians and several PhD students. MRD assessments may be hampered by the intra-tumor heterogeneity of AML, this and concurrent clonal evolution during therapy are also studied within the group of Prof. Cloos (Costa Bachas/ Diana Hanekamp). With the aim to target MRD and reduce the risk of relapse for the individual patient, drug resistance against standard chemotherapy and novel treatment strategies such as proteasome inhibitors and splicing modulators are also studied (Anna Wojtuszkiewicz).

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Participation in research collaborations

• Dutch AML MRD working party, chair

• European Leukemia Network, AML MRD working party, coordinator of the Flow cytometry group

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Research projects (and collaborators)

• Alternative splicing (profiles) as stem cell targeted treatment of acute myeloid leukemia, Diamond Program (Inge van der Werf), Prof. Dr. S. Zweegman, Hematology, Prof. Dr. GJL. Kaspers, Pediatric Oncology, Dr. R. Groen, Hematology

• Evaluation of the proteasome inhibitor Ixazomib against pediatric acute leukemia and Bortezomib-resistant leukemia cells, Prof. Dr. S. Zweegman, Hematology, Prof. Dr. GJL. Kaspers, Pediatric Oncology, Dr. G. Jansen, Rheumatology

• Identification of under-treated and over-treated acute myeloid leukemia patients, using minimal residual disease and leukemia stem cell frequency, Prof. Dr. G. Ossenkoppele, Hematology, Dr. GJ. Schuurhuis, Hematology

• Splicing as mechanism of drug resistance in Rheumatology and Acute lymphoblastic leukemia, Dr. G. Jansen, Rheumatology, Prof. Dr. R. de Jonge, Clinical Chemistry.

• Phosphoproteomics in acute myeloid leukemia, Dr. JJWM Janssen, Hematology and Prof. Dr. C. Jimenez, Medical Oncology

• Multi-Drug Resistance mechanisms in cancer: clinical response in patients with MDR and overcoming chemotherapy resistance with phytocannabinoids, Prof. Dr. GJ. Peters, Medical Oncology and Dr. G. Jansen, Rheumatology

• Add-on study to A Phase 3 randomized trial investigating Bortezomib (PS-341, Velcade) on a modified augmented BFM (ABFM) backbone in newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL), Dr. T. Horton (Baylor College of Medicine, Houston USA) and Dr. G. Jansen, Rheumatology

• Improvement of the survival of children with acute myeloid leukemia (projects of Stichting Egbers) Prof. Dr. GJL. Kaspers, Pediatric Oncology

 

​MRD studies

MRD measurements for >50 institutes in 12+ countries world wide

• HOVON/SAKK 145: Phase III Panobinostat after AlloSCT

• HOVON/SAKK 150: IDH1/2 inhibitors with standard chemo (IDH1/2 mutated)

• HOVON/SAKK 156: Phase III Gilteritinib vs Midostaurin + chemo (FLT3 mutated)

• MERUS MCLA117: Bispecific antibody therapy against CLEC12A

• Janssen AML2002: Bispecific antibody therapy against CD123 (Closed)

• Helsinn PRAN-16-52: Phase III Pracinostat

• Novartis PKC421E2301: Phase III Midostaurin in FLT3ITD-

• Novartis PKC412A2218: Phase II Midostaurin in FLT3ITD+ (children)

• Novartis MBG453B12201: Phase II MBG453 with hypomethylating agents (MDS)

• DCOne-002: Dendritic cell vaccination