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.
Fais
F
F
Human Anatomy Section, Department of Experimental Medicine, University of Genoa, Italy. franco.fais@unige.it
Tenca
C
C
Cimino
G
G
Coletti
V
V
Zanardi
S
S
Bagnara
D
D
Saverino
D
D
Zarcone
D
D
De Rossi
G
G
Ciccone
E
E
Grossi
C E
CE
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
D018949:Antigens, CD1; D055610:Antigens, CD1d; D014408:Biomarkers, Tumor; C526877:CD1D protein, human; D005699:Galactosylceramides; C493154:alpha-galactosylceramide