Relevance of leukemic stem cells in acute myeloid leukemia: heterogeneity and influence on disease monitoring, prognosis and treatment design

Acute myeloid leukemia is a bone marrow disease characterized by a block in differentiation of the myeloid lineage with a concomitant uncontrolled high proliferation rate. Development of acute myeloid leukemia from stem cells with specific founder mutations, leads to an oligoclonal disease that progresses into a very heterogeneous leukemia at diagnosis. Measurement of leukemic stem cell load and characterization of these cells are essential for prediction of relapse and target identification, respectively. Prediction of relapse by monitoring the disease during minimal residual disease detection is challenged by clonal shifts during therapy. To overcome this, characterization of the potential relapse-initiating cells is required using both flow cytometry and molecular analysis since leukemic stem cells can be targeted both on extracellular features and on stem-cell specific signal transduction pathways.