Anti-CD38 antibody - Mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells

David C. Taussig, Farideh Miraki-Moud, Fernando Anjos-Afonso, Daniel J. Pearce, Kirsty Allen, Christopher Ridler, Debra Lillington, Heather Oakervee, Jamie Cavenagh, Samir G. Agrawal, T. Andrew Lister, John G. Gribben, Dominique Bonnet

Research output: Contribution to journalArticlepeer-review

Abstract

Immunodeficient mice are increasingly used to assay human hematopoietic repopulating cells as well as leukemiainitiating cells. One method commonly used to isolate these rare cells is to sort cells stained with fluorochrome- conjugated antibodies into fractions, then transplant the different fractions into immunodeficient mice to test their repopulating ability. The antibodies are generally treated as being neutral in terms of their effects on the experiment. Human repopulating cells are thought to express CD34 and lack CD38. Here we present evidence that anti-CD38 antibodies have a profound inhibitory effect on engraftment of cord blood and leukemia cells. We show that this effect is Fc-mediated and can be overcome by treating mice with immunosuppressive antibodies. When this inhibitory effect is prevented, we demonstrate that the CD34+CD38+ fraction of certain acute myeloid leukemia samples contains all, or at least most, leukemiainitiating cell capacity. This study highlights the potential pitfall of antibodymediated clearance of repopulating cells and is important for any groups working with this model. More importantly, the work suggests that there is greater variation in the phenotypes of leukemiainitiating cells than previously suggested.

Original languageEnglish
Pages (from-to)568-575
Number of pages8
JournalBlood
Volume112
Issue number3
DOIs
StatePublished - 1 Aug 2008
Externally publishedYes

Fingerprint

Dive into the research topics of 'Anti-CD38 antibody - Mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells'. Together they form a unique fingerprint.

Cite this