Prognostic implications of blast self-renewal capacity in acute myelocytic-leukemia

The in vitro culture studies have revealed that the infinite proliferation of leukemic cells in acute myelocytic leukemia (AML) is supported by leukemic blast progenitors with self-renewal capacity. The self-renewal of blast progenitors is assessed by either secondary blast colony-formation in methylcellulose culture or clonogenic cell recovery in suspension culture. The patients whose leukemic blast progenitors had high self-renewal ability were more difficult in achieving complete remission and survived for shorter term than those with leukemic blast progenitors of low self-renewal capacity. Namely, the self-renewal capacity of leukemic blast progenitors was highly predictive of not only remission induction outcome but also survival duration of AML patients. Among several antileukemic agents tested, only a few drugs such as cytosine arabinoside were effective against blast self-renewal. To cure AML, a therapy that aims to eradicate self-renewing leukemic blast progenitors should be developed.