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Identification of a Set of Seven Genes for the Monitoring of Minimal Residual Disease in Pediatric Acute Myeloid Leukemia

Authors' Affiliations: ¹ University Children's Hospital Jena, Jena; ² University Children's Hospital Essen, Essen, ³ Clinical Genetics, Faculty of Medicine, University of Dresden, Dresden, Germany; and ⁴ Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland

Requests for reprints: Daniel Steinbach, University Children's Hospital Jena, Kochstrasse 2, 07740 Jena, Germany. Phone: 49-364-193-8270; Fax: 49-364-193-8306; E-mail: Daniel{at}Steinba.ch.

Background: Monitoring of minimal residual disease (MRD) has become a strong diagnostic tool in acute lymphoblastic leukemia. It is used for risk-adapted therapy and for the recognition of pending relapses. In acute myeloid leukemia (AML), there is still a need for more suitable MRD markers.

Experimental Design: A stepwise approach which combined genome-wide expression profiling, TaqMan low density arrays, and a TaqMan real-time PCR-based screening was used to identify new markers for the monitoring of MRD in AML. Leukemic cells from 52 children with AML and 145 follow-up samples from 25 patients were analyzed.

Results: Seven genes were identified which are vastly overexpressed in many patients with AML compared with healthy bone marrow: CCL23, GAGED2, MSLN, SPAG6, and ST18 as well as the previously described markers WT1 and PRAME. The expression of all genes decreased to normal levels in patients who achieved a continuous complete remission. Elevated levels of at least one gene were found prior to relapse in 7 out of 10 patients who relapsed.

Conclusions: This set of genes should allow a sensitive and specific monitoring of MRD in AML. Notably, some of these markers could also serve as therapeutic targets or might be involved in leukemogenesis. MSLN is already used as a target for immunotherapy in clinical trials in other malignancies.

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