• Biomarkers
  • AML
  • Precision medicine
  • Translational research (TRL 4-5)

Single-cell omics analysis platform to study longitudinal changes during the course of therapy (including during aplasia) in patients treated for acute myeloid leukemia (AML).

AML is characterized by its heterogeneity, and rare cell populations within the leukemic bulk can significantly impact treatment outcomes. Our single-cell omics analysis platform allows for a comprehensive profiling of individual leukemic cells, providing unparalleled precision and specificity. This level of detail helps in identifying unique biomarkers that may not be detectable with bulk analysis, thus offering a more accurate reflection of the disease state and treatment response.

Description

Scope of research activities

Translational research to analyze longitudinal changes in genotype or phenotype of leukemic and immune cells at single-cell resolution in AML patients undergoing therapy and discover predictive biomarkers through:

  • Single-cell omics (DNA, RNA, surface protein, methylation)
  • Functional flow cytometry assays (e.g. BH3 profiling, PgP efflux, SCENITH) coupled with analysis of surface protein expression
  • Including in rare subpopulations (LSCs) or non-leukemic cells (infiltrating T cells)
  • Analysis of fresh or viably frozen samples
  • Longitudinal monitoring including in hypocellular samples (e.g. drug-induced aplasia)

Conduct of studies

Steps:

  • Study design 
  • Define means/resources and propose schedule (steps, GO/NO-GO, cost estimate)
  • Study organization, implementation and conduct
  • Data analysis and delivery of a study report with recommendations

Research infrastructure

Experimental and analysis platforms :

  • Tapestri, Mission Bio
  • Chromium X, 10X Genomics
  • Automated liquid dispensing (Biomek i5, Beckmann Coulter)
  • Magnetic cell enrichment (MACS, Miltenyi)
  • Spectral cell sorting (BigFoot, ThermoFisher)
  • High-Throughput Screening flow cytometer (3 lasers, 13 parameters, iQUE3, Sartorius)
  • Conventional flow cytometer (2 lasers, 8 parameters, Cytoflex, Beckmann Coulter)

Models:

  • Primary cells from AML patients (including R/R AMLs; fully annotated – demographics, prior therapies & genetics)
  • Human AML cell lines (assay calibration)

Assays:

  • Single-cell DNA ± Surface Protein ± Targeted methylation
  • Single-cell DNA ± Surface Protein ± Chromatin Accessibility
  • Flow cytometry
  • BH3 profiling
  • PgP efflux
  • SCENITH
  • Apoptosis / Ferroptosis

Technical personel : 

  • 1 physician-scientist (scientific supervision, bioinformatics) and 1 operational engineer manager 
  • 1 engineer and 1 assistant engineer – flow cytometry & single-cell assays

Quality assurance

Université Paris Cité Technology Platforms certification (ongoing)

Specifications

The platform

Translational studies using primary cells from AML patients, for the analysis of dynamic changes in genetic or functional biomarker at single-cell resolution. 

The studies

Single-cell omics:

  • Clonal dynamics under therapy
  • Differentiation under therapy (with or without genetic information)
  • Changes in biomarker gene expression at single-cell resolution under therapy (leukemic cells or immune cells, including in the context of drug-induced aplastic bone marrow)  
  • LSC dynamics under therapy 

Functional flow cytometry:

  • Protein expression (surface or intracellular) at single-cell resolution and changes under therapy
  • BCL-2/BCL-xL/MCL-1 dependency and changes under therapy
  • OXPHOS/glycolysis dependency and changes under therapy
  • MDR phenotype (PgP activity) at single-cell resolution and changes under therapy
  • Apoptotic (Annexin V) or Ferroptotic (C11-BODIPY) cell death and changes under therapy

 

Examples of partnerships

Surface expression of an immunotherapy target on leukemic and residual leukemic cells – Surface expression of a biomarker in primary samples from R/R AML samples with clinical annotations, including differential expression in leukemic compartments (e.g. LSCs)

Partner: ADVESYA

 

Dynamics of resistance to venetoclax azacitidine – Longitudinal monitoring of changes in gene expression, BCL-2 dependency and metabolic changes during the first courses of venetoclax-based regimens in newly diagnosed AML.

Partner: INCa / DGOS (PRT-K)

Terms

OPALE entity

GenCellDis (UMR-944)

GenCellDis (UMR-944)
Raphaël Itzykson
Prof. Raphaël Itzykson

Contact

Sandrine Palcy Dr. Sandrine Palcy
Business Development Director

Other offers

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