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Laboratory of Hematopoietic Stem Cells and Leukemia - LSHL

UMR SGCSR - U1274

Published on 10 September 2019
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Associated unit 
UMR1274 INSERM/CEA/Université Paris 7/Université Paris 11

The team is also supported by l'Association pour la Recherche contre le Cancer (ARC) (Equipe labellisée, 2018-2020), by Institut du Cancer (Network « Cellular and Molecular Specificities of Pediatric Leukemia  », 2019-2021), by Association Laurette Fugain (2018-2019) and by Pôle Radiobiologie du CEA.
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​The blood cells are produced through the proliferation and differentiation of hematopoietic stem cells (HSC) and progenitors.
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HSC are defined by their quiescent state, their self-renewal and multipotential properties, that are regulated through a combination of intrinsic and extrinsic factors.

Genetic studies have unveiled the implication of transcription factors or of signaling pathways in HSC characteristics but the understanding of the connecting networks between those different pathways in normal hematopoiesis or in leukemic transformation still requires additional work.

Our laboratory is interested to understand the networks that connect these pathways in normal and malignant hematopoiesis

Genotoxic stress, in particular those generated through reactive oxygen species (ROS), induce cellular transformations, in particular in in hematopoietic cells. Hematopoiesis in adults is localized in the BM. HSC and progenitors are in close contact with specialized structures called "niches". These BM niches allow HSC to be maintained in quiescence and their perturbation can induce major deregulations in blood cell production. Intrinsic and extrinsic factors that regulate normal hematopoiesis are, for many of them, implicated into leukemic transformation. Recent publications clearly indicate that the deregulation of pathways, such as NOTCH for instance, in a niche component can induce haematological disorders.

Our laboratory is interested to learn more about the interactions between the medullar niche and leukemic blast cells.

Françoise PFLUMIO
Principal investigator
Phone : +33 (0)1 4​6 54 86 17

francoise.pflumio@cea.fr


Secretary of UMR SGCSR - U1274

Aurélie GOURET
Phone : +33 (0)1 46 54 98 66
aurelie.gouret@cea.fr

Arielle LELIARD
Phone : +33 (0)1 46 54 99 49
arielle.​leliard@cea.fr


​Research projects
Our main scientific goals are :
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  • To determine the consequences of ROS on the quiescence and self-renewal of human HSC. We wish to identify novel molecular players, and connect them to known pathways, for the control of HSC properties in normal and genetoxic stress conditions. We are testing the relation between the microenvironment and HSC in such stress conditions.



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  • To uncover the link between the microenvironment and the leukemia development in the case of T-cell acute leukemia (T-ALL). Our recent results show an important role of cells and factors secreted by the BM niche for the development of T-ALL. These data call for a better definition of the implicated cellular and molecular components.

  • To study the consequences of expressing fusion genes, described as major oncogenetic events in pediatric leukemias, in stem and progenitor cells from the human hematopoietic system. This work is done in collaboration with the laboratory of T Mercher, Gustave Roussy, Villejuif, France.

  • To (1)    To improve xenograft models of human normal and leukemic hematopoietic stem/progenitor cells by establishing human ossicles in immune-deficient mice.
Press review



Techniques / Skills / Equipment​
Our studies combine genetic, molecular and cellular approaches as well as imaging in human and mouse as well as in xenograft models of normal human hematopoiesis and leukemia using immune-deficient mice.

​Collaborations

Marjorie Brand, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Canada.
Andréas Reinisch, Medical University of Graz, Graz, Austria.
Olivier Bernard, INSERM U1170, Institut Gustave Roussy, Villejuif, France.
Thomas Mercher, INSERM U1170, Institut Gustave Roussy, Villejuif, France.
Michaela Fontenay et Olivier Kosmider, INSERM U1016, Institut Cochin, Paris, France .
Marc Berger, Groupe Hématologie de EA 7283 – CREaT, Clermont-Ferrand, France.
Pablo Menendez, Jose Carreras Leukemia Research Institute, Barcelone, Espagne.
Ronan Quéré, Université de Bourgogne, Dijon, France.
Christine Bourgeois, UMR 1184, Kremlin-Bicêtre, France.



Part of the CONNECT-AML network