Relapse of acute myeloid leukaemia (AML) can arise owing to the presence of one of two distinct populations of leukaemia cells according to a study published online in Nature this week. The identification of different patterns of relapse could lead to improved methods for disease management and monitoring of AML.
In AML, long-term survival is poor as most patients relapse after remission of the cancer. However, the mechanisms of therapy failure and the capacity for leukaemic regeneration have been difficult to identify.
Using samples of mononuclear blood cells collected from 11 patients with AML at diagnosis and relapse, John Dick and colleagues identified therapy-resistant cells already present at diagnosis and two distinct pathways resulting in the relapse of this cancer. In some patients (defined as having a primitive relapse origin), relapse occurred owing to the presence of a rare population of leukaemia stem cells, already present at diagnosis prior to the initiation of therapy. Conversely, in other patients (relapse origin-committed cases), relapse developed because of a group of leukaemia cells that have retained transcriptional signatures of stem cells. The findings suggest that relapse in both patient groups is linked to the stem cell properties of the cells identified.
The findings support the idea that therapeutic strategies for AML must not only eradicate bulk tumour cells, but also effectively target cancer stem cells.