INVESTIGATING THE MECHANISM OF ACTION OF DRUG CANDIDATES FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA

Preclinical development
Functional studies

Targeted therapy
Immunotherapy
Chemotherapy

Preclinical research (TRL 4-5)

Translational studies to identify the mechanism of action of drug candidates for the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Discovery of mechanisms of action in cell line models.

Validation in primary human AML and MDS cells.

Description

Scope of research activities

Preclinical research for the proof of concept of the mechanism of action of new molecules in in vitro models of MDS and AML:

Biomarker research
Research into synthetic lethality pathways

Conducting studies

Steps:

Establishment of cell line models by target invalidation
Analysis of intracellular modifications
Search for synthetic lethal pathways
Validation in primary human leukemia cells in vitro and in vivo in PDX
Analysis and communication of results

Research infrastructure

Experimental and analytical platforms:

CYBIO cytometry platform
IMAG'IC confocal imaging platform
GENOM'IC transcriptomic analysis platform
PROTEOM'IC proteomic analysis platform
EOPS animal facilities (human cell xenograft models in immunocompetent mice)

Models:

Hematopoietic cell lines
Primary cells from AML patients
Primary cells from MDS patients

Technical personnel:

1 assistant engineer
1 research technician

Quality assurance

Institut Cochin Genomics (DNA-seq, RNA-seq, methylation) platform - GENOM'IC : ISO 9001 - IBISA certifications .

Institut Cochin Proteomics platform - PROTEOM'IC: ISO 9001/NF X 50-900 - IBISA certifications.

Specifications

The platform

Translational research platform for in vitro studies of the mechanism of action of drug candidates on primary cells from MDS and AML patients.

The studies

Mechanism of action of the drug candidate's anti-leukemic activity:

Analysis of mitochondrial metabolic pathways and cell death pathways

Examples of partnerships

Biological studies of phase 2 clinical trial IMerge - Evaluation of gene expression profile of bone marrow mononuclear cells and of peripheral blood immune cell populations upon treatment. In vitro effect of MDS erythropoiesis.

Partner: GERON

Terms

OPALE entity

Cochin Institute (UMR-1016)

**Prof. Didier Bouscary**
Head of Entity

Contact