10 cutting-edge research projects
The largest challenge associated with leukemia treatment is persistence of residual therapy-resistant cancer cells, called minimal residual disease (MRD), which underlies disease relapse and is responsible for the low survival rates of patients. Currently, knowledge on mechanisms of persistence of MRD and initiation of leukemia relapse is lacking, making development of therapeutics eradicating MRD difficult and hampering improvement of patient cure rates.
The MIRACLE network will take an integrated, multidisciplinary and intersectoral approach to address the key unresolved questions on the molecular and cellular basis of acute leukemia MRD.
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DC1: Optimizing treatment decisions by using MRD data combined with artificial intelligence.>
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DC2: In-depth analysis of phenotypic acute leukemia MRD dynamics using single sell data and advance computational techniques >
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DC3: The establishment of clinical translational AML MRD on-chip models >
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DC4: Characterization of AML MRD using single cell transcriptomic and epigenetic analysis >
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DC5: The characterization of acute lymphoblastic leukemia MRD and relapse using single cell omics >
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DC6: Multiomic and metabolomic characterization of AML residual disease after AZA/VEN treatment >
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DC7: Dissecting and targeting niche-dependent vulnerabilities of protection from therapy in AML >
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DC8: Therapy-induced senescence as anti-cancer and immune-stimulatory strategy in AML >
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DC9: Characterization of persisting leukemic blasts in down syndrome patients to define targets for immune-therapy >
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DC10: Targeting MRD and LSCs in the bone marrow niche by chemokine modified, dual targeting CAR T cells in AML >
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).
The MIRACLE 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.