METABOLIC, GENOMIC, TRANSCRIPTOMIC AND FUNCTIONAL ANALYSES OF THE LEUKEMIC NICHE FOR PHASE 1 TRIALS (MPN/ALL/AML/MDS)

Clinical development

Targeted therapy
Precision medicine
Chemotherapy

Clinical research (TRL 6-8)

The Biological Hematology Department of the CHRU de Tours (Prof. Olivier HERAULT) brings its expertise in chemoresistance mechanisms and its metabolic, genomic, transcriptomic and functional analysis platforms for Phase I clinical trials in leukemia.

The Biological Hematology Department develops, performs, interprets and monitors specialized cellular hematology examinations for the whole of the Tours University Hospital, and more widely for the Centre region in the fields of hematological malignancies and hematopoietic stem cell transplants.

Description

Scope of research activities

Clinical research in AML, MNP, MDS and ALL pathologies, with the aim of improving patient care and quality of life:

Interventional research: early clinical trials for new therapeutic approaches

Role

Participation in drafting the clinical protocol for biological analyses
Analysis design
Organization, implementation and conduct of analyses
Interpretation and communication of results

Infrastructure

Experimental and analysis platforms:

Hypoxia and intramedullary pressure modeling stations (Avatar®)
Flow cytometry: FACS (BD Melody®)
Real-time metabolic analysis (Seahorse®, Omnilog®)
Single cell analysis systems (including Chromium Controller 10X Genomics)
Genomic, transcriptomic, metabolomic, lipidomic analyses

Models:

Primary cells from clinical study patients, with FACS sorting possibilities within the entity to study subpopulations of interest

Technical personnel:

4 PhD engineers
3 technicians

Quality assurance

Analyses performed in a COFRAQ-accredited hospital laboratory; clinical-grade analyses with exclusive intra-CHU circuit (clinical departments, Clinical Investigation Centre, biological haematology department).

Specifications

The platform

Metabolic analyses (energetic/oxidative) coupled with genomic, transcriptomic and functional analyses of leukemic niche players (hematopoietic cells, mesenchymal stromal cells) for Phase I trials, using patients' primary cells (marrow, blood).

The studies

Evaluation of drug candidate toxicity:

Analyses of cell cycle, apoptosis, DNA breaks
Analyses of oxidative metabolism (ROS quantification by CMF, antioxidograms, NRF2 pathway, MAPK signalling) and energy metabolism (glycolysis, oxidative phosphorylation)
Transcriptomic (RNAseq, scRNAseq, RT-qPCR), genomic (NGS mutational profiles) and epigenomic (DNA methylation) analyses
Functional analyses (hematopoietic progenitor cultures, LTC-IC in limiting dilution, MSC differentiation)

Terms

Clinical research project with industrial promotion
Partnership agreement with study sponsor

OPALE entity

U1069-N2COx

**Prof. Olivier Hérault**
Head of Entity

Contact

Other offers

IN VITRO EVALUATION OF THE EFFECTS OF ANTILEUKEMIC DRUGS IN A MODELED LEUKEMIC NICHE WITH OPTIMIZED BONE MARROW MICROENVIRONMENT (MSCS, HYPOXIA, PRESSURE) (MPN/ALL/AML/MDS)