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 Blood, 1 October 2007, Vol. 110, No. 7, pp. 2659-2666.
Prepublished online as a Blood First Edition Paper on July 3, 2007; DOI 10.1182/blood-2007-03-083048.

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NEOPLASIA

The novel AML stem cell–associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells

Anna van Rhenen1, Guus A. M. S. van Dongen2, Angèle Kelder1, Elwin J. Rombouts3, Nicole Feller1, Bijan Moshaver1, Marijke Stigter-van Walsum2, Sonja Zweegman1, Gert J. Ossenkoppele1, and Gerrit Jan Schuurhuis1

1 Department of Hematology and 2 Department of Otolaryngology, VU [Vrije Universiteit] University Medical Center, Amsterdam; 3 Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands

In CD34+ acute myeloid leukemia (AML), the malignant stem cells reside in the CD38– 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 nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with outgrowth to CLL-1+ blasts. CLL-1 expression was not different between diagnosis and relapse (n = 9). In remission, both CLL-1– normal and CLL-1+ malignant CD34+CD38– cells were present. A high CLL-1+ 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.


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