DEVELOPMENT OF NEW TARGETED THERAPIES FOR ACUTE MYELOID LEUKEMIA

Target discovery

Targeted therapy

Basic research (TRL 1-3)

Studies for the development of targeted therapies in Acute Myeloid Leukemia (AML) based on the identification of new molecular abnormalities in tumors.

The identification and characterization of molecular anomalies, combined with the search for biomarkers, enable us to propose new therapeutic targets for the treatment of AML. In collaboration with the Clinical Hematology Department of Bordeaux University Hospital, the new variants identified can be evaluated, within the framework of translational projects, as molecular markers for the prognosis and follow-up of residual disease.

Description

Scope of research activities

Studies to identify new therapeutic targets for the treatment of AML:

Target identification and characterization
Signaling studies
Biomarker research
Functional analysis

Conduct of studies

Steps :

Study design after defining the question to be answered
Proposal of a timetable based on the stages involved
Implementation of schedule and experiments
Conducts of experiments and analyses of results
Study report by experimenters

Research infrastructure

Experimental and analysis platforms:

Flow cytometry, vectorology and imaging platforms
Tissue physioxia culture platform
A2 animal facility

Models:

AML mouse models
Patient-derived xenograft (PDX) murine models AML
Primary cells from AML patients

Technical personnel:

2 engineers
1 technician

Quality assurance

All platform members have undergone quality assurance training, and several platforms are certified.

Specifications

The studies

Target identification and characterization:

Genome-wide CrispR screening to identify genes involved in treatment response or resistance
Target validation and modeling

Signaling studies:

Western-blot analysis and characterization, flow cytometry and functional testing of signaling pathways
In vitro modeling of signaling pathways

Biomarker research:

Cohort analysis (PCR-Q, NGS, flow cytometry)

Functional analysis:

In vitro and ex vivo validation of response and/or resistance in physioxic systems
In vivo validation in an immunodeficient mouse model (PDX LAM)

Examples of partnerships

In vitro and in vivo functional validation of Giltéritinib in FLT3-ITD AML - Recent development of dual inhibitor against FLT3 and AXL allow to treat ederly patients, to get deeper response but no change in overall survival. We identify a new cell subpopulation persistent in the hematopoietic niche.

Partner: Astellas Pharma

Search for a novel FLT3 isoform in AML patients - Identification of new oncogenic isoform of FLT3 in resistant AML lead to characterize the response to FLT3 inhibitors of this isoform and to identify it as a prognostic marker.

Partner: Bristol Meyrs Squibb