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

F Fais·C Tenca·G Cimino·V Coletti·S Zanardi·D Bagnara·D Saverino·D Zarcone·G De Rossi·E Ciccone·C E Grossi
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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, alpha-galactosylceramide (alpha-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 alpha-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 alpha-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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Antigens, CD1Antigens, CD1dB-LymphocytesBiomarkers, TumorCell CommunicationCell LineChildGalactosylceramidesHematopoietic Stem CellsHumansInfantKiller Cells, NaturalPrecursor Cell Lymphoblastic Leukemia-LymphomaPredictive Value of TestsPrognosisSurvival RateJournal ArticleResearch Support, Non-U.S. Gov't

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F Fais, C Tenca, G Cimino, V Coletti, S Zanardi, D Bagnara, D Saverino, D Zarcone, G De Rossi, E Ciccone, C E Grossi. 2005. CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis.. https://doi.org/10.1038/sj.leu.2403671

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