CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia.

Abstract

Permanent cure of acute myeloid leukemia (AML) by chemotherapy alone remains elusive for most patients because of the inability to effectively eradicate leukemic stem cells (LSCs), the self-renewing component of the leukemia. To develop therapies that effectively target LSC, one potential strategy is to identify cell surface markers that can distinguish LSC from normal hematopoietic stem cells (HSCs). In this study, we employ a signal sequence trap strategy to isolate cell surface molecules expressed on human AML-LSC and find that CD96, which is a member of the Ig gene superfamily, is a promising candidate as an LSC-specific antigen. FACS analysis demonstrates that CD96 is expressed on the majority of CD34(+)CD38(-) AML cells in many cases (74.0 +/- 25.3% in 19 of 29 cases), whereas only a few (4.9 +/- 1.6%) cells in the normal HSC-enriched population (Lin(-)CD34(+)CD38(-)CD90(+)) expressed CD96 weakly. To examine whether CD96(+) AML cells are enriched for LSC activity, we separated AML cells into CD96(+) and CD96(-) fractions and transplanted them into irradiated newborn Rag2(-/-) gamma(c)(-/-) mice. In four of five samples, only CD96(+) cells showed significant levels of engraftment in bone marrow of the recipient mice. These results demonstrate that CD96 is a cell surface marker present on many AML-LSC and may serve as an LSC-specific therapeutic target.

• Authors: Naoki Hosen, Christopher Y Park, Naoya Tatsumi, Yusuke Oji, Haruo Sugiyama, Martin Gramatzki, Alan M Krensky, Irving L Weissman
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 26 Pg. 11008-13 (Jun 26 2007) ISSN: 1091-6490 [Electronic] United States
• PMID: 17576927 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Biomarkers
• CD96 antigen
• Neoplasm Proteins

Topics

• Acute Disease
• Animals
• Antigens, CD
• Biomarkers
• Flow Cytometry
• Graft Survival
• Humans
• Leukemia, Myeloid (pathology)
• Mice
• Mice, Knockout
• Neoplasm Proteins (analysis)
• Neoplasm Transplantation
• Neoplastic Stem Cells (chemistry, pathology)
• Transplantation, Heterologous