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UMR - 1274

The team Niche and cancer in hematopoiesis, directed by Françoise Pflumio, is supported by Inserm, CEA, University of Paris and University Paris-Saclay. 

The entity is interested in the molecular mechanisms that drive transformation and propagation of leukemic cells in mouse and humans, the interactions between the bone marrow microenvironment and the normal and pathologic cells, and myeloproliferative syndromes.

Image UMR - 1274
Françoise Pflumio
Dr. Françoise Pflumio

Head of Entity

Contact

Email : francoise.pflumio@cea.fr

Institute of Cellular and Molecular Radiobiology (IRCM) CEA,
18, route du Panorama
92260 FONTENAY-AUX-ROSES - France

Website

  • Acute Lymphoblastic Leukemia (ALL)
  • Acute Myeloid Leukemia (AML)

Normal hematopoiesis

  • Role of macrophages in the resistance of hematopoietic stem cells (HSC) to ionizing radiations
  • Impact of antioxidants on the potential of human HSC
  • Effects of low doses of radiation in HSC
  • Modeling of humanized bone marrow niches in vivo

Pathological hematopoiesis

  • Mechanisms of chemoresistance in T-ALL : impact of the BM micro-environment 
  • Mechanisms of transformation related to specific genetic events in T-ALL: search for new therapeutic strategies
  • Impact of inflammation in the development of T-ALL
  • Search for of acute leukemia initiating cells in children pathologies

 

  • Targeted therapy
  • Cell therapy
  • Chemotherapy

Scientific 

  • Development of in vivo models for normal human hematopoiesis using immune deficient mice (Lapi.dot et al, Science, 1994; Pflumio F et al., Blood, 1996)
  • Study of the efficacy of lentiviral vector transduction of human hematopoietic stem/progenitor cells and T-ALL (Sirven et al., Blood, 2000; Sirven et al., Mol Ther, 2001; Amsellem S et al., Mol Ther, 2002; Gerby et al., Leukemia, 2010) 
  • Development of in vitro and in vivo conditions supporting human T-ALL growth: impact of the Notch pathway- study of disease development in PDX mice (Armstrong F et al., Blood, 2009; Poglio, Oncotarget, 2016; Clappier E et al. JEM, 2011; Gerby et al., Leukemia, 2011)
  • Study of the niche factors in growth and chemoresistance of human T-ALL (Uzan B et al, Embo Mol Med, 2014; Cahu X et al, Blood Advances, 2017)
  • Role of transcription factors TAL1 and TLX3 in T-ALL development and normal human HSC (Ravet e et al, Blood, 2004; Reynaud D et al, Blood, 2005; Kusy et al, JEM, 2010)
  • Impact of low and high irradiation doses on human HSC (Chabi S et al, Int J Radiat Oncol Biol Phys, 2021; Barroca V et al, Leukemia, 2022; Henry E et al, Haematologica, 2020)

  • Allouch, A., Voisin, L., Zhang, Y., Raza, S.Q., Lecluse, Y., Calvo, J., Selimoglu-Buet, D., de Botton, S., Louache, F., Pflumio, F., Solary, E., Perfettini, J.-L., 2022. CDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia. Nat Commun 13, 6739. https://doi.org/10.1038/s41467-022-34548-3
  • Arcangeli, M.-L., Brault, P., Bourhis, J.-H., Kuhnowskie, F., Henry, E., Barroca, V., Koscielny, S., Pflumio, F., Amsellem, S., 2020. Combined G-CSF and Plerixafor enhance hematopoietic recovery of CD34+ cells from poor mobilizer patients in NSG mice. Exp Hematol 86, 15-20.e2. https://doi.org/10.1016/j.exphem.2020.05.006
  • Barroca, V., Henry, E., Dechamps, N., Renou, L., Chaintreuil, P., Kulkarni, R., Devanand, S., Jacquel, A., Robert, G., Auberger, P., Pflumio, F., Arcangeli, M.-L., 2022. REDD1 is a gatekeeper of murine hematopoietic stem cell functions during stress responses. Leukemia 36, 2140–2143. https://doi.org/10.1038/s41375-022-01609-x
  • Cahu, X., Calvo, J., Poglio, S., Prade, N., Colsch, B., Arcangeli, M.-L., Leblanc, T., Petit, A., Baleydier, F., Baruchel, A., Landman-Parker, J., Junot, C., Larghero, J., Ballerini, P., Delabesse, E., Uzan, B., Pflumio, F., 2017. Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia. Blood Adv 1, 1760–1772. https://doi.org/10.1182/bloodadvances.2017004960
  • Calvo, J., Fahy, L., Uzan, B., Pflumio, F., 2019. Desperately seeking a home marrow niche for T-cell acute lymphoblastic leukaemia. Adv Biol Regul 74, 100640. https://doi.org/10.1016/j.jbior.2019.100640
  • Chabi, S., To, T.H.V., Leavitt, R., Poglio, S., Jorge, P.G., Jaccard, M., Petersson, K., Petit, B., Roméo, P.-H., Pflumio, F., Vozenin, M.-C., Uzan, B., 2020. Ultra-high-dose-rate FLASH and Conventional-Dose-Rate Irradiation Differentially Affect Human Acute Lymphoblastic Leukemia and Normal Hematopoiesis. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2020.10.012
  • Chabi, S., Uzan, B., Naguibneva, I., Rucci, J., Fahy, L., Calvo, J., Arcangeli, M.-L., Mazurier, F., Pflumio, F., Haddad, R., 2019. Hypoxia Regulates Lymphoid Development of Human Hematopoietic Progenitors. Cell Rep 29, 2307-2320.e6. https://doi.org/10.1016/j.celrep.2019.10.050
  • Chesnais, V., Arcangeli, M.-L., Delette, C., Rousseau, A., Guermouche, H., Lefevre, C., Bondu, S., Diop, M., Cheok, M., Chapuis, N., Legros, L., Raynaud, S., Willems, L., Bouscary, D., Lauret, E., Bernard, O.A., Kosmider, O., Pflumio, F., Fontenay, M., 2017. Architectural and functional heterogeneity of hematopoietic stem/progenitor cells in non-del(5q) myelodysplastic syndromes. Blood 129, 484–496. https://doi.org/10.1182/blood-2016-03-707745
  • Henry, E., Souissi-Sahraoui, I., Deynoux, M., Lefèvre, A., Barroca, V., Campalans, A., Ménard, V., Calvo, J., Pflumio, F., Arcangeli, M.-L., 2020. Human hematopoietic stem/progenitor cells display reactive oxygen species-dependent long-term hematopoietic defects after exposure to low doses of ionizing radiations. Haematologica 105, 2044–2055. https://doi.org/10.3324/haematol.2019.226936
  • Renou, L., Boelle, P.-Y., Deswarte, C., Spicuglia, S., Benyoucef, A., Calvo, J., Uzan, B., Belhocine, M., Cieslak, A., Landman-Parker, J., Baruchel, A., Asnafi, V., Pflumio, F., Ballerini, P., Naguibneva, I., 2017. Homeobox protein TLX3 activates miR-125b expression to promote T-cell acute lymphoblastic leukemia. Blood Adv 1, 733–747. https://doi.org/10.1182/bloodadvances.2017005538

Research infrastructures

Genetic engineering

 

Institute of Cellular and Molecular Radiobiology (IRCM)

CIGEx: platform of genetic engineering and expression, including scRNAseq analysis - Principal investigator: Didier Busso.

 

Cytometry

 

Institute of Cellular and Molecular Radiobiology (IRCM)

The Cytometry and Cell Sorting facility provides instrumentation and technical expertise, for the development of collaborative projects involving flow cytometric analysis and cell sorting - Principal investigator: Jan Baijer and Annette Schmitz.

 

Irradiation

 

Institute of Cellular and Molecular Radiobiology (IRCM)

The irradiation platform is opened to labs which study the effect of ionizing radiations. This platform is open also to outside labs, which need to irradiate their organic or non-organic samples - Principal investigator: Véronique Ménard.

 

Microscopy

Institute of Cellular and Molecular Radiobiology (IRCM)

The platform provides researchers of the institute, the necessary equipment and expertise in light microscopy for any scientific project in life sciences using the techniques of cell imaging - Principal investigator: Lamya Irbah.

 

Transcriptomics

Platform of transcriptome analysis - Principal investigators: D. Lewandowski, A. Chicheportiche, M.J. Guerquin.

 

Animal facility

 

Animal facility – Principal investigator: S Vincent-Naulleau

Platform of animal experimentation – Principal investigator: V Barroca

 

Protein analysis

 

Platform of protein analyses (WES (protein Simple), BioPlex (BioRad)) – Principal investigators: D.Lewandowski, Xavier Veaute.

 

Biological samples

 

Cohort

AML

 

Xenografts of human AML, especially children samples.

Cells from AML patients.

Cohort

ALL

Xenografts of human T-ALL, especially children samples.

Cells from T-ALL and B-ALL patients.

 
Category Models Pathology Specification Sample type Number of models Genetics characterization
In vitro Human primary cells T-ALL - Diagnosis - -
In vitro Human primary cells T-ALL - Relapse - -
In vitro Mouse tumor-derived cell line T-ALL ICN1 - - -
In vitro Mouse tumor-derived cell line T-ALL TAL1/LMO1 - - -
In vivo PDX AML - - 8 Some
In vivo PDX T-ALL - - 57 Some
In vivo PDX B-ALL - - 8 All

Partnership research offers

PRECLINICAL STUDIES FOR THE DEVELOPMENT OF INNOVATIVE TREATMENTS FOR ACUTE LYMPHOBLASTIC LEUKEMIA

PRECLINICAL STUDY OF HEMATOPOIETIC SYSTEM REGENERATION FOLLOWING EXPOSURE TO GENOTOXIC STRESS SUCH AS IRRADIATION AND CHEMOTHERAPY (ALL/AML)

PRECLINICAL TESTING OF CAR-T CELLS FOR THE TREATMENT OF T/B ACUTE LYMPHOBLASTIC LEUKEMIA

Partners

Academics

Affiliation

CEA Inserm Université Paris Cité Université Paris Saclay