Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemia

Autor: Felix Zintl, Masanori Onda, Astrid Voigt, Daniel Steinbach, Kristin Dawczynski, Alexander Schramm, Angelika Eggert, Susann Wittig, Andreas Rump, Ira Pastan, Nadine Pfaffendorf, Bernd Gruhn
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Popis: 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.
Databáze: OpenAIRE