title: CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis.
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.
authors.affiliation: Human Anatomy Section, Department of Experimental Medicine, University of Genoa, Italy. franco.fais@unige.it
authors.forename: F
authors.initials: F
authors.lastname: Fais
authors.forename: C
authors.initials: C
authors.lastname: Tenca
authors.forename: G
authors.initials: G
authors.lastname: Cimino
authors.forename: V
authors.initials: V
authors.lastname: Coletti
authors.forename: S
authors.initials: S
authors.lastname: Zanardi
authors.forename: D
authors.initials: D
authors.lastname: Bagnara
authors.forename: D
authors.initials: D
authors.lastname: Saverino
authors.forename: D
authors.initials: D
authors.lastname: Zarcone
authors.forename: G
authors.initials: G
authors.lastname: De Rossi
authors.forename: E
authors.initials: E
authors.lastname: Ciccone
authors.forename: C E
authors.initials: CE
authors.lastname: Grossi
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000166:cytology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D002648:Child; D005699:Galactosylceramides / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D014408:Biomarkers, Tumor; C526877:CD1D protein, human; D005699:Galactosylceramides; C493154:alpha-galactosylceramide