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Childhood ALL

CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis

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Abstract

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Although therapeutical advances have been achieved, some ALL subgroups still fare poorly. CD1d is a monomorphic molecule that provides a suitable target for immunotherapy in view of the characterization of a glycolipid, α-galactosylceramide (α-GalCer), capable of being presented to CD1d-restricted T cells with cytotoxic potential. We investigated CD1d expression in 80 pediatric B-cell precursor (BCP) ALL cases defined according to immunophenotype, cytogenetic features and age at onset. CD1d was detected on ALL cells in 15% of the patients. CD1d+ ALLs were significantly associated with infant leukemia, pro-B phenotype and mixed-lineage leukemia (MLL)/AF4 gene rearrangement. Accordingly, overall survival of patients with CD1d+ ALL was significantly shorter. CD1d+ leukemic blasts were able to present α-GalCer via CD1d to cytotoxic CD1d-restricted T cells, which induced apoptosis of ALL cells that was inhibited by mAb to CD1d. CD1d+ blasts loaded with α-GalCer elicited cytokine secretion by CD1d-restricted T cells. Analysis of bone marrow (BM) cells derived from normal donors revealed that CD19+/CD1d+ cells were mostly mature B lymphocytes. However, a minority of BCPs expressed CD1d. Thus, expression of CD1d in ALL cases heralds an adverse prognosis but may provide a therapeutic tool.

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Acknowledgements

This work was supported by grants from Ministero per l'Istruzione l'Università e la Ricerca Scientifica (MIUR), Progetto Finalizzato, Ministero della Salute (‘Alterazioni Geniche nelle Leucemie Acute’) and Compagnia di S Paolo, Torino, to CEG and EC.

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  1. F Fais and C Tenca: These authors have contributed equally to the work

Authors and Affiliations

  1. Human Anatomy Section, Department of Experimental Medicine, University of Genoa, Italy

    F Fais, C Tenca, D Bagnara, D Saverino, D Zarcone, E Ciccone & C E Grossi

  2. Section of Hematology, Department of Cellular Biotechnology and Hematology, University ‘La Sapienza’, Rome, Italy

    G Cimino

  3. Department of Pediatric Haematology and Oncology, Ospedale Bambino Gesù, Rome, Italy

    V Coletti & G De Rossi

  4. Section of Biostatistics, Department of Health Sciences, University of Genoa, Italy

    S Zanardi

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  1. F Fais
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  2. C Tenca
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  3. G Cimino
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  4. V Coletti
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  5. S Zanardi
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  6. D Bagnara
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  7. D Saverino
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  8. D Zarcone
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  9. G De Rossi
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  10. E Ciccone
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  11. C E Grossi
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Correspondence to F Fais.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Fais, F., Tenca, C., Cimino, G. et al. CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis. Leukemia 19, 551–556 (2005). https://doi.org/10.1038/sj.leu.2403671

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  • DOI: https://doi.org/10.1038/sj.leu.2403671

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