Molecular Mechanisms of Acute Myeloid Leukemia Development

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Alexandre Puissant

His team was created in 2017,labeled ATIP-AVENIR (2017–2020), then ERC StG (2018–2024), and more recently ERC CoG (2024–2029).

Stéphanie CHAMBAUD

Research themes

Research themes

The team focuses on

  • understanding the complex biology of acute myeloid leukemias (AML) and
  • discovering promising therapeutic approaches aimed at optimizing responses to existing targeted therapies and frontline treatments.

To do this, we deploy large-scale screening strategies, functional genomics, and proteomics applied to preclinical murine models (xenografts from syngeneic mice and patient-derived xenografts, PDX). Leveraging our expertise in AML biology and advanced functional genomics and large-scale in vivo screening tools, our research program revolves around three projects.

  • Acute myeloid leukemias (AML)
  • Malignant hematological diseases

Research areas

By deploying large-scale functional screening approaches, we assess in mouse models the functional relevance of metabolic and epigenetic drivers in enabling leukemic blasts to progress toward malignancy, independently of mutational variations and clonal heterogeneity.

We apply bioinformatics and biostatistical methodologies derived from artificial intelligence to syngeneic mouse models, combined with deep sequencing of serial patient samples (diagnosis/relapse), to refine the evolutionary trajectories of leukemic clones from initiation to treatment resistance. This allows us to identify adaptive dead-ends that transformed cells are forced to enter, which can be targeted for eradication.

We have developed the RAINBOW program, which leverages functional precision medicine biomarkers based on flow cytometry to improve patient care pathways and identify new therapeutic repositioning strategies or novel drug combinations. This multiparametric pharmacological screening approach, conducted under pseudo-niche conditions, assesses in the context of first-in-human clinical trials (relapsed or refractory patients) the surface antigen expression or preclinical activity of new compounds or combinations on clinically and genetically annotated primary patient samples, including within defined target populations.

Members of Alexandre Puissant's team

Alexandre Puissant
Team leader, Inserm DR2, HDR
Nina Fenouille
Project Manager, Inserm CRCN
Thierry Tchenio
Inserm CRCN, HDR
Lionel Ades
PU-PH, HDR
Thorsten Braun
PU-PH, HDR
Raphaël Itzykson
PU-PH, HDR
Marie Sebert
PU-PH, HDR
Matthieu Duchmann
AHU, CCA Inserm-Bettencourt
Kevin Boumeghar
Master 2 Student
Lucie Freiman
PhD 1st year
Gerasimos Tsilimidos
Visiting Clinical Fellow
Carine Legrand
Postdoc, OPALE Carnot Institute
Caique Lopes Souza
Postdoc, Inserm CDD
Khansa Saadallah
Postdoc, Inserm CDD
Nuria Alvarez Pizarroso
PhD 4th year
Nicolas Lecornec
PhD 2nd year
Lois Kelly
PhD 4th year
Léa Pelissier Menjaud
PhD 2d year
Chloé Zédouard
PhD 2d year
Juliette Charles
Assistant Engineer, Inserm CDD
Morgane Fontaine
Research Engineer, AP-HP CDD
Catherine Longchamp
Assistant Engineer, Inserm CDD
Kim Pacchiardi
Research Engineer, AP-HP CDD

Scientific publications

Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer (en translation)

Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer

Kevin H. Lin & al, Nature Genetics, 2020
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Targeting a lineage-specific PI3Kɣ–Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule

Targeting a lineage-specific PI3Kɣ–Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule

Lois M. Kelly & al, Nature Cancer, 2024
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P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia

P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia

Kevin H. Lin & al, Nature Cancer, 2022
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Job offers

Portrait Chercheur

Biological Assistant Engineer

participating in a project on myeloid leukemias, using cellular and molecular techniques and murine experimentation.

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Portrait Chercheur

Post-doctoral Fellow

Post-doctoral Fellow leading a project on the study of AML development.

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Financements

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