CD34 expression in native human acute myelogenous leukemia blasts: Differences in CD34 membrane molecule expression are associated with different gene expression profiles

Background: The stem cell marker CD34 is expressed by leukemia blasts only for a subset of patients with acute myelogenous leukemia (AMIL). It is still controversial as to whether CD34 expression (defined as at least 10-20% positive cells) has any prognostic effect in patients with AML who receive intensive chemotherapy. The present study investigated whether gene expression profiling could be used to further subclassify CD34(+) AML cell populations. Methods: AML blasts derived from 25 patients were examined; these patients were randomly selected from a larger consecutive group of patients. CD34 protein expression was determined by flow cytometry and expressed as the percentage of positive cells. Gene expression profiles were determined by complementary DNA microarrays. Results: By unsupervised hierarchical clustering our patients could be grouped into two or three major subsets depending on the methodologic approach before clustering analysis (filtering or flooring of data, respectively). However, both approaches identified a cluster characterized by high gene expression and membrane molecule level of CD34. When using the floored expression profiles, the patient cluster characterized by increased CD34 gene expression was also characterized by a high percentage of CD34+ cells (median 82%, range 56-100%) compared with the two other major clusters (median 19%, range <1-55%), but three of four outpatients also showed a high percentage of CD34+ cells. Conclusion: A major proportion of patients with AML and high CD34 expression (usually >80% COW cells; nearly all patients had >50% positive cells) showed similarities in gene expression profile. In contrast, patients with lower CD34 expression often had a profile similar to those of patients regarded as CD34(-) according to conventional criteria. Our results suggest that the possible prognostic effect of CD34 expression should be reevaluated in clinical studies using additional or alternative cutoff values to describe CD34 expression. (C) 2005 Wiley-Liss, Inc.