Portal de Periódicos da CAPES

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

2007; Elsevier BV; Volume: 110; Issue: 7 Linguagem: Inglês

10.1182/blood-2007-03-083048

1528-0020

Anna van Rhenen, Guus A.M.S. van Dongen, Angèle Kelder, Elwin Rombouts, N Feller, Bijan Moshaver, Marijke Stigter-van Walsum, Sonja Zweegman, Gert J. Ossenkoppele, Gerrit Jan Schuurhuis,

Chronic Lymphocytic Leukemia Research

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.