ATLANTAThe malignant stem cells believed to develop into cells associated with acute myeloid leukemia (AML) appear to be distinguishable from normal stem cells with the use of a novel antigen marker, Gerrit Jan Schuurhuis, PhD, said at the 2005 American Society of Hematology annual meeting (abstract 4). Dr. Schuurhuis is associate professor of hematology, VU University Medical Center, Amsterdam, The Netherlands.
The genesis of CD34-positive AML is thought to occur at the CD34+CD38- stem cell stage. In patients receiving chemotherapy for AML, a high frequency of these AML precursors is associated with more frequent minimal residual disease and poor survival. Therefore, identification and monitoring of these cells could be beneficial in predicting clinical outcomes and monitoring success of therapy.
Dr. Schuurhuis and his colleagues previously found that a monoclonal antibody directed against the myeloid-specific C-type lectin-like molecule-1 (CLL-1) stained diagnosed AML at a sensitivity of 92%. In the current study, they further characterized CLL-1 expression in CD34+CD38- stem cells of patients at different stages of treatment for AML.
Of the 89 patients evaluated at the time of diagnosis, the anti-CLL-1 antibody stained the CD34+CD38- compartment in 77 cases (86.5%). The median CLL-1 expression across all 89 patients was 33.3% of all stem cells (range, 0% to 100%). Median expression in control bone marrow was 0% (range, 0% to 11%). CLL-1 expression profiles did not change between diagnosis and relapse in the 12 paired samples tested (P = .9)
The investigators evaluated the relative frequency of leukemic (CLL-1-positive) and normal (CLL-1-negative) stem cells in remission bone marrow of patients with varying clinical outcomes following treatment for AML. The ratio of AML to normal stem cells turned out to correlate with clinical outcomes: Patients with a high proportion of malignant stem cells had a poor remission quality and fast relapses, whereas those with relatively few malignant stem cells had responded well to treatment.
The normal stem cells under no relevant condition gained CLL-1 expression during treatment: CLL-1 was not detected on CD34+CD38- cells in the regenerating bone marrow following high-dose chemotherapy of either patients with CLL-1-negative AML at diagnosis or patients with nonmyeloid malignancies. In contrast to CLL-1, expression of the AML stem cell marker CD123 did not appear to specifically mark AML stem cells in remission bone marrow.
Given its specificity for the stem cells associated with AML, not only does anti-CLL-1 appear to provide a sensitive means of detecting malignant stem cells, but as ASH president James George, MD, noted, "it provides a key new and potentially very effective target for chemotherapy" for the treatment of AML.