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 |
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Jazyk: | angličtina |
Rok vydání: | 2006 |
Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Neoplasm Residual Adolescent medicine.medical_treatment Medizin GPI-Linked Proteins Antigens Neoplasm Bone Marrow hemic and lymphatic diseases Internal medicine TaqMan Biomarkers Tumor Medicine Humans Child WT1 Proteins Oligonucleotide Array Sequence Analysis PRAME Membrane Glycoproteins business.industry Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Infant Newborn Myeloid leukemia Infant Immunotherapy medicine.disease Minimal residual disease Gene expression profiling DNA-Binding Proteins Repressor Proteins Leukemia medicine.anatomical_structure Leukemia Myeloid Chemokines CC Child Preschool Mesothelin Immunology Acute Disease Microtubule Proteins Female Bone marrow business |
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 |
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