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Acute Leukemias

Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations

Leukemia volume 25, pages 1249–1258 (2011)Cite this article

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Abstract

Leukemia-initiating/repopulating cells (LICs), also named leukemic stem cells, are responsible for propagating human acute leukemia. Although they have been characterized in various leukemias, their role in T-cell acute lymphoblastic leukemia (T-ALL) is unclear. To identify and characterize LICs in T-ALL (T-LIC), we fractionated peripheral blood cell populations from patient samples by flow cytometry into three cell fractions by using two markers: CD34 (a marker of immature cells and LICs) and CD7 (a marker of early T-cell differentiation). We tested these populations in both in vitro culture assays and in vivo for growth and leukemia development in immune-deficient mice. We found LIC activity in CD7+ cells only as CD34+CD7− cells contained normal human progenitors and hematopoietic stem cells that differentiated into T, B lymphoid and myeloid cells. In contrast, CD34+CD7+ cells were enriched in LICs, when compared with CD34−CD7+ cells. These CD34+CD7+ cells also proliferated more upon NOTCH activation than CD34−CD7+ cells and were sensitive to dexamethasone and NOTCH inhibitors. These data show that CD34 and CD7 expression in human T-ALL samples help in discriminating heterogeneous cell populations endowed with different LIC activity, proliferation capacity and responses to drugs.

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Acknowledgements

We acknowledge all the patients and their parents for providing samples for our studies. Cell sorting was performed by the flow cytometry platform of IRCM with the help of N Dechamps and J Baijer (Fontenay-aux-Roses, France). C Joubert, J Tilliet and V Neuville in IRCM provided excellent animal colony care. BG received a fellowship from the Ligue Nationale Contre le Cancer and from the Société Française d’Hématologie. EC is a fellow of Institut du Cancer (INCA). FA was paid by the CreMEC consortium. This work was supported by grants from INSERM, CEA, Université Paris 7, Association Laurette Fugain, INCA and the Cancéropole, Ile de France.

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Authors and Affiliations

  1. Laboratoire des Cellules Souches Hématopoïétiques et Leucémiques, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), UMR967 INSERM, Université Paris 7, Université Paris 11, Commissariat à l’Energie Atomique (CEA), Fontenay-aux-Roses, France

    B Gerby, E Clappier, F Armstrong, C Deswarte, J Calvo, S Poglio, P Ballerini & F Pflumio

  2. Département de Génétique, Hôpital Robert Debré, AP-HP, Paris, France

    E Clappier

  3. Service d’Hématologie et d’Oncologie Pédiatrique, Hôpital A Trousseau AP-HP/Université Pierre et Marie Curie—Paris 6, Paris, France

    C Deswarte & J Landman-Parker

  4. Equipe Remaniements du Génome et Cancers, INSERM U944 et Laboratoire d’Hématologie AP-HP, Institut Universitaire d’Hématologie Université Paris Diderot, Hôpital Saint-Louis, Paris, France

    J Soulier

  5. Services d’Hématologie Pédiatrique et d’Hématologie Adulte, Hôpital Saint-Louis et Robert Debré, AP-HP, Paris, France

    N Boissel, T Leblanc & A Baruchel

  6. Laboratoire de la Régulation de la Transcription des cellules Souches, Institut de Radiobiologie Cellulaire et Moléculaire, Inserm U967, Université Paris 7, Commissariat à l’Energie Atomique (CEA), Fontenay-aux-Roses, France

    P H Roméo

  7. Service d’Hématologie Biologique, Hôpital Trousseau AP-HP, Université Pierre et Marie Curie, Paris, France

    P Ballerini

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  1. B Gerby
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Correspondence to F Pflumio.

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Author contributions

BG, EC, FA, CD, SP and JC performed experiments; BG, EC, PB and FP designed the experiments, analyzed the results and wrote the manuscript; JS and PHR helped with critical experiments and with writing the manuscript; NB, TL, AB, JLP and PB provided patient samples and shared crucial informations.

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Gerby, B., Clappier, E., Armstrong, F. et al. Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations. Leukemia 25, 1249–1258 (2011). https://doi.org/10.1038/leu.2011.93

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