Brief Communication

Acute lymphoblastic leukemia

Saracatinib impairs maintenance of human T-ALL by targeting the LCK tyrosine kinase in cells displaying high level of lipid rafts

Published online:
  • Subscribe to Leukemia for full access:



Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.


  1. 1.

    Cramer SD, Aplan PD, Durum SK. Therapeutic targeting of IL-7Ralpha signaling pathways in ALL treatment. Blood. 2016;128:473–8.

  2. 2.

    Ratajczak MZ, Adamiak M. Membrane lipid rafts, master regulators of hematopoietic stem cell retention in bone marrow and their trafficking. Leukemia. 2015;29:1452–7.

  3. 3.

    Tamarit B, Bugault F, Pillet AH, Lavergne V, Bochet P, Garin N, et al. Membrane microdomains and cytoskeleton organization shape and regulate the IL-7 receptor signalosome in human CD4 T-cells. J Biol Chem. 2013;288:8691–701.

  4. 4.

    Hermiston ML, Xu Z, Majeti R, Weiss A. Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases. J Clin Invest. 2002;109:9–14.

  5. 5.

    Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000;1:31–9.

  6. 6.

    Mollinedo F, de la Iglesia-Vicente J, Gajate C, Estella-Hermoso de Mendoza A, Villa-Pulgarin JA, Campanero MA, et al. Lipid raft-targeted therapy in multiple myeloma. Oncogene. 2010;29:3748–57.

  7. 7.

    Mollinedo F, de la Iglesia-Vicente J, Gajate C, Estella-Hermoso de Mendoza A, Villa-Pulgarin JA, de Frias M, et al. In vitro and In vivo selective antitumor activity of Edelfosine against mantle cell lymphoma and chronic lymphocytic leukemia involving lipid rafts. Clin Cancer Res. 2010;16:2046–54.

  8. 8.

    Gajate C, Mollinedo F. Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts. Blood. 2007;109:711–9.

  9. 9.

    Gajate C, Gonzalez-Camacho F, Mollinedo F. Involvement of raft aggregates enriched in Fas/CD95 death-inducing signaling complex in the antileukemic action of edelfosine in Jurkat cells. PLoS ONE. 2009;4:e5044.

  10. 10.

    Gajate C, Mollinedo F. Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy. J Biol Chem. 2005;280:11641–7.

  11. 11.

    Reis-Sobreiro M, Gajate C, Mollinedo F. Involvement of mitochondria and recruitment of Fas/CD95 signaling in lipid rafts in resveratrol-mediated antimyeloma and antileukemia actions. Oncogene. 2009;28:3221–34.

  12. 12.

    Schubbert S, Cardenas A, Chen H, Garcia C, Guo W, Bradner J, et al. Targeting the MYC and PI3K pathways eliminates leukemia-initiating cells in T-cell acute lymphoblastic leukemia. Cancer Res. 2014;74:7048–59.

  13. 13.

    De Keersmaecker K, Porcu M, Cox L, Girardi T, Vandepoel R, de Beeck JO, et al. NUP214-ABL1-mediated cell proliferation in T-cell acute lymphoblastic leukemia is dependent on the LCK kinase and various interacting proteins. Haematologica. 2014;99:85–93.

  14. 14.

    Ivanyi P, Morgan M, Piao W, Ukena SN, Steube K, Ganser A, et al. Pre T-cell receptor alpha (pTalpha) expression patterns and functional analysis in human T-cell lymphoblastic leukemia. Cell Oncol. 2010;32:101–8.

  15. 15.

    Serafin V, Lissandron V, Buldini B, Bresolin S, Paganin M, Grillo F, et al. Phosphoproteomic analysis reveals hyperactivation of mTOR/STAT3 and LCK/Calcineurin axes in pediatric early T-cell precursor ALL. Leukemia. 2017;31:1007–11.

Download references


We are grateful to Sébastien Causse for his help with the microscopy, Jean-Paul Pais de Barros for the lipidomic study, Julien Guy for help with T-ALL sample characterization and Philip Bastable for editing and critical reading of this manuscript. This study was supported by grants from the association Laurette Fugain (RQ), the Conférence de Coordination Interrégionale du Grand Est—Bourgogne Franche-Comté (CCIRGE-BFC) de la Ligue contre le Cancer (RQ), by the National Research Agency under the program “Investissements d’Avenir” (reference ANR-11-LABX-0021, LipSTIC Labex), by the Conseil Régional de Bourgogne through the plan d’action régional pour l’innovation (PARI) and the European Union through the PO FEDER-FSE Bourgogne 2014/2020 programs. AB was supported by fellowships from the French Ministère de la Recherche et de l’Enseignement Supérieur (MRES) and LS-P by a fellowship from the Conseil Régional de Bourgogne/INSERM. FP and BU have grants from LNCC, INSERM, CEA, and Université Paris Diderot.

Author contributions

AB and RQ conceived the experiments, performed the experiments, and interpreted the data; TA helped with the experiments; LS-P performed the isolation of rafts by flotation on sucrose density gradients; GL performed the proteomic study; J-NB and LD discussed the data; BU and FP provided human T-ALL xenografts and advices in the usage of such models and discussed the data; LD and FP helped with the writing of the manuscript; AB and RQ wrote the manuscript; RQ supervised the research.

Author information


  1. UMR1231, Inserm / Université Bourgogne Franche-Comté, Dijon, France

    • Anne Buffière
    • , Théo Accogli
    • , Laetitia Saint-Paul
    • , Jean-Noël Bastie
    • , Laurent Delva
    •  & Ronan Quéré
  2. Labex LipSTIC, Dijon, France

    • Anne Buffière
    • , Laetitia Saint-Paul
    • , Jean-Noël Bastie
    • , Laurent Delva
    •  & Ronan Quéré
  3. Plateforme de Protéomique, Université Bourgogne Franche-Comté, Dijon, France

    • Géraldine Lucchi
  4. UMR967, Inserm / CEA / Université Paris 7 / Université Paris 11, Fontenay-aux-Roses, France

    • Benjamin Uzan
    •  & Françoise Pflumio
  5. LSHL, IRCM / CEA, Fontenay-aux-Roses, France

    • Benjamin Uzan
    •  & Françoise Pflumio
  6. Assistance Publique-Hôpitaux de Paris, Laboratoire d’Hématologie, Hôpital Trousseau, Paris, France

    • Paola Ballerini
  7. Hôpital Universitaire François Mitterrand, Service d’Hématologie Clinique, Dijon, France

    • Jean-Noël Bastie
  8. Hôpital Universitaire François Mitterrand, CRB Ferdinand Cabanne, BB-0033-00044, Dijon, France

    • Jean-Noël Bastie


  1. Search for Anne Buffière in:

  2. Search for Théo Accogli in:

  3. Search for Laetitia Saint-Paul in:

  4. Search for Géraldine Lucchi in:

  5. Search for Benjamin Uzan in:

  6. Search for Paola Ballerini in:

  7. Search for Jean-Noël Bastie in:

  8. Search for Laurent Delva in:

  9. Search for Françoise Pflumio in:

  10. Search for Ronan Quéré in:

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Ronan Quéré.

Electronic supplementary material