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

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.