Submitted March 30, 2007
Accepted June 29, 2007
The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells
Anna van Rhenen, Guus A.M.S. van Dongen, Angele Kelder, Elwin J. Rombouts, Nicole Feller, Bijan Moshaver, Marijke Stigter-van Walsum, Sonja Zweegman, Gert J. Ossenkoppele, and Gerrit Jan Schuurhuis*
Dept of Hematology, VU University Medical Center, Amsterdam, Netherlands
Dept of Otolaryngology, VU University Medical Center, Amsterdam, Netherlands
Dept of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands
* Corresponding author; email: gj.schuurhuis{at}vumc.nl.
In CD34 positive AML the malignant stem cells reside in the CD38 negative compartment. We have shown before that the frequency of such CD34+CD38- cells at diagnosis correlates with minimal residual disease (MRD) frequency after chemotherapy and with survival. Specific targeting of CD34+CD38- cells might thus offer therapeutic options. Previously we found that C-type lectin-like molecule-1 (CLL-1) has high expression on the whole blast compartment in the majority of AML cases. We now show that CLL-1 expression is also present on the CD34+CD38- stem cell compartment in AML (77/89 patients). The CD34+CLL-1+ population, containing the CD34+CD38-CLL-1+ cells, does engraft in NOD/SCID mice with outgrowth to CLL-1 positive blasts. CLL-1 expression was not different between diagnosis and relapse (n=9). In remission, both CLL-1 negative normal and CLL-1 positive malignant CD34+CD38- cells were present. A high CLL-1 positive fraction was associated with quick relapse. CLL-1 expression is completely absent both on CD34+CD38- cells in normal (n=11) and in regenerating bone marrow controls (n=6). This AML stem cell specificity of the anti-CLL-1 antibody under all conditions of disease and the leukemia-initiating properties of CD34+CLL-1+ cells, indicate that anti-CLL-1 antibody enables both AML-specific stem cell detection and possibly antigen-targeting in future.
