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

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. Experim...

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Veröffentlicht in:Clinical cancer research 2006-04, Vol.12 (8), p.2434-2441
Hauptverfasser: STEINBACH, Daniel, SCHRAMM, Alexander, ZINTL, Felix, GRUHN, Bernd, EGGERT, Angelika, ONDA, Masanori, DAWCZYNSKI, Kristin, RUMP, Andreas, PASTAN, Ira, WITTIG, Susann, PFAFFENDORF, Nadine, VOIGT, Astrid
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Sprache:eng
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Zusammenfassung: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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-05-2552