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, Angè Le Kelder, Elwin J. Rombouts, Nicole Feller, Bijan Moshaver, Marijke Stigter Van Walsum, Sonja Zweegman, Gert J. Ossenkoppele, Gerrit Jan Schuurhuis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)2659-2666
Number of pages8
Issue number7
Publication statusPublished - 1 Oct 2007

Cite this