Unsupervised Hierarchical Clustering of Surface Antigen Expression to Identify Patients with Normal Karyotype AML with Distinct Disease Characteristics and Poor Outcome

There is limited understanding of the biologic and prognostic implications of surface antigen expression patterns in patients with normal karyotype acute myeloid leukemia (AML). Researchers sought to understand the relationship between surface antigen expression and molecular disease features.

The diagnostic antigen expression patterns of mononuclear cells in the bone marrow of 111 patients with normal karyotype AML were assessed using a standard flow cytometric panel. All patients received stem-cell transplantation after induction therapy. The median follow-up was 3.3 years. Hierarchical clustering of surface antigens revealed 4 distinct clusters of surface antigens. Cluster 1 (n = 36) had higher expression of immature surface antigens; cluster 2 (n = 31) had higher expression of surface antigens of thrombocytic or erythroid origin; cluster 3 (n = 24) had higher expression of monocytic surface antigens; and cluster 4 (n = 20) had higher expression of granulocytic surface antigens.

All 4 clusters showed distinct clinical and molecular features. Most notably, patients with high expression of immature surface antigens had a higher cumulative incidence of relapse at 1 year (41% vs 15%; P = 0.002) and shorter event-free survival at 1 year (50% vs 69%; P = 0.02). In multivariate analysis, differences persisted after adjustment for FLT3 mutation status, age, and disease status at the time of stem-cell transplant.

The researchers identified a relationship between easily accessible surface antigen expression patterns at diagnosis, molecular disease features, and aggressiveness of the normal karyotype AML phenotype.

Jentzsch M, et al. ASCO Abstract 7042.

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