Combat minimal residual disease (MRD) to revolutionize leukemia treatment

MIRACLE is a Marie Skłodowska-Curie doctoral network aiming to educate a new generation of researchers optimally equipped to advance and accelerate development of novel therapeutics directed to leukemia MRD, and to progress effective treatments to the clinic. The project will investigate the leukemia MRD landscape by integrating the knowledge on mechanisms driving persistence of MRD from different angles, and by the subsequent design of efficient and less toxic, novel targeted combination therapy with increased capacity to induce deep responses in patients. 

Our mission

  • Improve the lives of cancer patients and increase their survival chances by addressing one of the greatest challenges in leukemia treatment; the persistence of therapy-resistant cancer cells, known as minimal residual disease (MRD). 
  • Conduct 10 outstanding research projects
  • Guide 10 talented doctoral candidates to become creative entrepreneurial scientists in the first dedicated MCSA DN about leukemia.

Integrated multi-angle research and training network to eradicate leukemia minimal residual disease. 

MIRACLE-Leukemia will address one of the greatest challenges in leukemia treatment; the persistence of therapy-resistant cancer cells, known as minimal residual disease (MRD). 10 PhD students and their supervisors will tackle the problem of MRD in an integrated collaborative effort to prevent MRD-induced leukemia relapses and to drastically increase survival chances of leukemia patients. 

Despite advancements in cancer research, a lack of understanding of the mechanisms behind MRD persistence and relapse has hindered progress in developing effective therapies. Adding to this challenge is the fragmented expertise on MRD across Europe and a lack of multidisciplinary scientists capable of integrating insights from transcriptomics, epigenetics, metabolism, and immunology. Moreover, there has been thus far no dedicated doctoral training program tackling the problem of leukemia MRD. 

By employing 10 highly talented doctoral candidates, the MIRACLE-Leukemia consortium aims to execute cutting-edge studies in several academic and industrial institutes while training the PhD students in multidisciplinary and transferable skills. The 10 researchers will work on individual research projects and benefit from a comprehensive program that contains scientific, technical, and entrepreneurial training. MIRACLE-Leukemia will not only generate impactful research but also actively contribute to Europe’s Mission Cancer goal of increasing cure rates and improving the lives of cancer patients. The project aims to raise public awareness, influence policy, and create a lasting legacy in leukemia treatment. 

The 10 research projects collectively focus on advancing the understanding and treatment of acute leukemia MRD by leveraging cutting-edge techniques such as artificial intelligence, single-cell omics, multiomic and metabolomic profiling, identification of niche-dependent MRD vulnerabilities, in vivo CRISPR-CAS9 screening and epigenetic single cells analysis. The studies aim to optimize treatment decisions, develop translational organ-on-chip 3D MRD models, and design immune-based therapeutic approaches such as CAR T cells homing to the bone marrow and directed to  therapy-induced senescence, persistent leukemic blasts in Down syndrome patients, acute leukemia MRD and leukemic stem cells (LSCs). Together, the 10 researchers will address the key unresolved questions on the molecular and cellular basis of acute leukemia MRD and bridge preclinical and clinical research to come up with novel ideas on how to eradicate MRD and improve patient outcomes.

MIRACLE is an international, multidisciplinary and multisectoral training program consisting of 23 academic and non-academic partners from 8 EU countries The Netherlands, Belgium, Germany, France, Spain, Italy, Czech Republic, United Kingdom). The project is coordinated by Dr. Linda Smit and Prof. Jacqueline Cloos of the Amsterdam UMC department of Hematology. 

MIRACLE-Leukemia is a European project funded by the European Union’s Horizon Europe’s Research and Innovation Program under the Marie Sklodowska-Curie Actions Grant Agreement nr. 101167512.

MIRACLE Work Packages

The MIRACLE doctoral network is organized into seven interconnected work packages (WPs) that together address the challenge of minimal residual disease (MRD) in leukemia. Through cutting-edge research, training, and collaboration across Europe, these work packages aim to understand how therapy-resistant leukemia cells survive treatment and to develop innovative strategies to eliminate them.

 WP1 – LEARN: Training, PhD and Career Development

Lead: Amsterdam UMC

WP1 provides the doctoral training programme for MIRACLE researchers. Doctoral candidates receive interdisciplinary training in leukemia biology, advanced technologies, data science, and translational research, complemented by transferable skills training, mentoring, and international secondments in both academic and industrial settings.

WP2 – MRD Dynamics, Data Integration and AI

Lead: Charles University

WP2 focuses on understanding how minimal residual disease evolves during and after treatment. Using advanced bioinformatics, artificial intelligence, and single-cell data, this work package analyzes MRD dynamics to improve prediction of relapse and guide personalized treatment strategies.

 

WP3 – Transcriptomic and Epigenetic Drivers of MRD

Lead: VIB-KU Leuven

WP3 investigates the gene expression and epigenetic mechanisms that allow leukemia cells to survive therapy and persist as MRD. Using state-of-the-art single-cell multi-omics technologies, researchers identify molecular pathways that drive therapy resistance and potential targets for new anti-MRD treatments.

WP4 – Metabolic and Microenvironmental Mechanisms of MRD

Lead: INSERM

WP4 studies how metabolic adaptations and interactions with the bone marrow microenvironment enable leukemia cells to resist treatment. By combining single-cell transcriptomics, metabolomics, and experimental models, this work package aims to uncover vulnerabilities that can be targeted to eliminate MRD.

 WP5 – Immune-Based Therapies Targeting MRD

Lead: LMU Munich

WP5 explores immunotherapeutic strategies to eradicate residual leukemia cells. Researchers investigate immune responses against MRD and develop innovative approaches, including CAR-T cell strategies and immune-modulating therapies, to enhance the immune system’s ability to eliminate therapy-resistant leukemia cells

WP6 – NAVIGATE: Project Management and Coordination

Lead: Amsterdam UMC

WP6 ensures the effective coordination and management of the MIRACLE network, supporting collaboration between partners, monitoring progress, and ensuring that scientific, training, and administrative objectives are successfully achieved.

 WP7 – SHARE: Dissemination, Communication and Impact

Lead: Amsterdam UMC

WP7 focuses on sharing MIRACLE’s results with the scientific community, clinicians, patients, and society. Activities include dissemination of research findings, outreach to patient communities, communication through digital platforms, and strategies to translate scientific discoveries toward clinical applications.