Prognostic significance of the blast self-renewal capacity in patients with acute myeloid leukemia

Abstract

The proliferation of leukemic cells in acute myeloid leukemia (AML) is supported by a small subpopulation of leukemic blast progenitors, which can be detected in methylcellulose and suspension cultures. It is important to determine the association between the biologic properties of leukemic blast progenitors and the clinical prognosis of patients with AML. Ninety-five patients with AML and two patients with chronic myelocytic leukemia in blast crisis were studied. T-cell depleted mononuclear cells obtained from the peripheral blood cells were cultured in both methylcellulose and suspension cultures. In methylcellulose culture, primary blast colony formation (PE1) and secondary blast colony formation (PE2) were enumerated. The recovery of clonogenic cells was determined in suspension culture. The association between PE1, PE2, or clonogenic cell recovery in suspension and the remission induction outcome or survival duration of the patients were examined. PE1 was not associated with the remission induction outcome. PE2 and clonogenic cells recovered in suspension were significantly associated with the remission induction. Furthermore, the survival duration of the patients who achieved complete remission was associated significantly with the number of clonogenic cells recovered in suspension. PE1 reflects the terminal divisions of leukemic blast progenitors, whereas PE2 and the recovery of clonogenic cells in suspension culture are considered to reflect the self-renewal of leukemic blast progenitors. The results suggest that the self-renewal capacity of leukemic blast progenitors is predictive of not only remission induction outcome but also survival duration of patients with AML.