Aldehyde dehydrogenase activity among primary leukemia cells is associated with stem cell features and correlates with adverse clinical outcomes

Objective Animal models have provided evidence for the existence of leukemia stem cells (LSC). However, prospective isolation of human LSC from patients with acute myeloid leukemia (AML), as well as the assessment of their clinical significance, has remained a major challenge. Materials and Methods We have studied the functional characteristics of a subset of leukemia cells that expressed CD34 and high aldehyde dehydrogenase activity (ALDH br ), which was freshly isolated from the mononuclear cells at the time of diagnosis from the marrow of 68 consecutive patients suffering from AML. Results The percentage of ALDH br cells ranged from 0.01% to 16.0% with a median of 0.5%. Compared to their counterparts with low aldehyde dehydrogenase activity from the same individual patients, the ALDH br population showed a significantly higher affinity to human mesenchymal stromal cells (n=12; p p p p br cells correlated significantly with diminished survival probability ( p =0.025) and with adverse cytogenetic factors ( p Conclusion A small proportion of leukemia cells derived from the marrow of patients with AML were ALDH br and CD34 + . They demonstrated functional characteristics of LSC and high percentages of these cells among the leukemia cells correlated significantly with poor clinical outcome.