Submitted April 25, 2008
Accepted January 8, 2009
Expression of CD133 on leukemia initiating cells in childhood ALL
Charlotte V. Cox, Paraskevi Diamanti, Roger S. Evely, Pamela R. Kearns, and Allison Blair*
Bristol Institute for Transfusion Sciences, University of Bristol, Bristol, United Kingdom
Department of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
Bristol Haematology and Oncology Centre, Bristol, United Kingdom
Division of Reproductive and Child Health, University of Birmingham, Birmingham, United Kingdom
* Corresponding author; email: allison.blair{at}nbs.nhs.uk.
Optimization of therapy for childhood acute lymphoblastic leukemia (ALL) requires a greater understanding of the cells that proliferate to maintain this malignancy, since a significant number of cases relapse due to failure to eradicate the disease. Putative ALL stem cells may be resistant to therapy and subsequent relapses may arise from these cells. We investigated expression of CD133, CD19 and CD38 in pediatric B-ALL. Cytogenetic and molecular analyses demonstrated that karyotypically aberrant cells were present in both CD133+/CD19+ and CD133+/CD19- subfractions, as were most of the antigen receptor gene rearrangements. However, ALL cells capable of long-term proliferation in vitro and in vivo were derived from the CD133+/CD19- subfraction. Moreover, these CD133+/CD19- cells could self-renew to engraft serial NOD/SCID recipients and differentiate in vivo to produce leukemias with similar immunophenotypes and karyotypes as observed in the diagnostic samples. Furthermore, these CD133+/CD19- ALL cells were more resistant to treatment with dexamethasone and vincristine, key components in childhood ALL therapy, than the bulk leukemia population. Similar results were obtained using cells sorted for CD133 and CD38, with only the CD133+/CD38- subfraction demonstrating NOD/SCID repopulating capacity. These data suggest that leukemia initiating cells in childhood B-ALL have a primitive CD133+/CD19- and CD38- phenotype.
