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EMiLy (INSERM U1160)

The Team 1 “Homeostatic and Pathological Chemokine-Regulated Interplays between Lymphocytes and their Microenvironment” focuses its research on the following fields: immunology, hematology, oncology, bone marrow microenvironment in health and leukemic diseases.

Image EMiLy (INSERM U1160)
Karl Balabanian
Dr. Karl Balabanian

Head of Entity

Marion Espéli
Dr. Marion Espéli
Nicolas Dulphy
Dr. Nicolas Dulphy

Contact

Email : karl.balabanian@inserm.fr

Hôpital Saint Louis
Institut Recherche Saint Louis (IRSL)
1, avenue Claude Vellefaux
75010 PARIS - France

Website

  • Waldenström Macroglobulinemia (WM)
  • Acute Myeloid Leukemia (AML)
  • Myelodysplastic Syndromes (MDS)

One priority of INSERM U1160 in the scope of CARNOT is the study of immune contexture in myeloid malignancies, with a focus on the immune and non-immune stromal bone marrow environment, innate lymphoid cells development and anti-leukemic immune responses.

We are also characterizing through dedicated mouse models and human samples the cell intrinsic and cell extrinsic factors involved in Waldenström Macroglobulinemia development and prognostic.

  • Targeted therapy
  • Cell therapy
  • Immunotherapy

Scientific

  • INSERM U1160 described mechanisms responsible for defective Natural Killer (NK) cell-mediated immunosurveillance in AML and MDS.
  • The team put in light the role for MDS associated mutations in the perturbation of NK cell immunity. 
  • The team participated to the description of the immune contexture in MDS/CMML associated with systemic inflammatory and autoimmune disease.
  • The team demonstrated that a WHIM and Waldenstrom associated-Cxcr4 gain of function mutation leads to uncontrolled B cell extrafollicular response.
  • The team, together with clinical services at Hospitals Saint Louis, Necker and La Pitié-Salpétrière, also uncovers that inflammation in Waldenström patients is predictive of good outcome upon BTK inhibitor treatment.

Medical 

  • INSERM UMRS1160 has long-standing experience in terms of private-public collaborations for immunological and hematological studies in the frame of the development of new molecules or of clinical trials. 

 

  • Debureaux PE et al. Inflammation is predictive of outcome in Waldenström macroglobulinemia treated by Bruton tyrosine kinase inhibitors: a multicentric real-life study. Haematologica. 2023 Aug 17. doi: 10.3324/haematol.2023.283141. PMID: 37584289.
  • Boy M et al. Myelodysplastic Syndrome associated TET2 mutations affect NK cell function and genome methylation. Nat Commun. 2023 Feb 3;14(1):588. doi: 10.1038/s41467-023-36193-w. PMID: 36737440. 
  • Anginot A et al. WHIM Syndrome-linked CXCR4 mutations drive osteoporosis. Nat Commun. 2023 Apr 12;14(1):2058. doi: 10.1038/s41467-023-37791-4. PMID: 37045841.
  • Zhao LP et al. Genomic landscape of MDS/CMML associated with systemic inflammatory and autoimmune disease. Leukemia. 2021 Sep;35(9):2720-2724. doi: 10.1038/s41375-021-01152-1. PMID: 33623140.
  • Alouche N et al. Hematologic disorder-associated Cxcr4 gain-of-function mutation leads to uncontrolled extrafollicular immune response. Blood. 2021 Jun 3;137(22):3050-3063. doi: 10.1182/blood.2020007450. PMID: 33512437.

Research infrastructures

Cytometry

IRSL - Technology platform

3 missions:

  • Theoretical and practical training in the technology
  • Access to calibrated instruments (sorters and analyzers)
  • Personalized support for the design of experiments and results analysis 

 
Genomics

IRSL - Technology platform

The main mission of the Genomics Department is to meet the needs for genomic studies related to laboratory research activities and to be open to the entire academic (INSERM, CNRS, Universities, APHP) and industrial scientific community.

 
Microscopy

IRSL - Technology platform

Microscopy Department provides easy access and personalized support to modern optical microscopy techniques: confocal and multiphoton microscopy, wide-field microscopy, video-microscopy (multipoint and high-throughput timelapse).

 
Data center

IRSL - Technology platform

BioData Center Department provides a dual mission: support in setting up the IT tools necessary for the bio-informaticians of the Research teams, an infrastructure for calculation and analysis as well as for storage.

 
Animal facility

IRSL - Animal facility

The Department of Preclinical Models is a common service whose main mission is to meet the needs for animal experimentation relating to the scientific activity of the IRSL in compliance with the national and European regulations in force (Directive 2010/63; Decree 2013-118).

 

Immunomonitoring

Immunomonitoring platform.

Biological samples

 

Various sources

AML

MDS

WM

 

Center of Biological Resources of Saint-Louis (CRB Saint-Louis).

 
Category Models Pathology Specification Sample type Number of models Genetics characterization
In vitro Organoids MSD/AML 3D Model (Artificial BM organoid) NK cells/MSC/blastes - - -
In vivo Mouse model Waldenström's macroglobulinemia Cxcr4+/1013 x Myd88B-L252P =Waldenstrom-like disease - - -
In vivo Mouse model Richter's Syndrome Cxcr4+/1013xEµ-TCL1=CLL/Richter syndrome like disease - - -

Partnership research offers

DEVELOPMENT OF IMMUNOTHERAPIES TARGETING THE CYTOTOXIC ACTIVITY OF NK CELLS (ALL/MDS)

IN VIVO MODEL OF WALDENSTRÖM DISEASE

STUDY OF IMMUNE CELL BIOLOGY IN RESPONSE TO TREATMENT IN AML/MDS/WM PATIENTS

Partners

Academics

Affiliation

Inserm Université Paris Cité