Project description:Identification of Acquired Copy Number Alterations and Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia Using High-Resolution Single Nucleotide Polymorphism Analysis Recent advances in genome-wide single nucleotide polymorphism (SNP) analyses have revealed previously unrecognized microdeletions and uniparental disomy (UPD) in a broad spectrum of human cancers. As acute myeloid leukemia (AML) represents a genetically heterogeneous disease, this technology might prove helpful especially for cytogenetically normal AML (CN-AML) cases. Thus, we performed high-resolution SNP analyses in 157 adult cases of CN-AML. Regions of acquired UPD were identified in 12% of cases and most frequently affected chromosomes 6p, 11p, and 13q. Notably, acquired UPD was invariably associated with mutations in NPM1 or CEBPA that impair hematopoietic differentiation (P=0.008), suggesting that UPDs may preferentially target genes that are essential for proliferation and survival of hematopoietic progenitors. Acquired copy number alterations (CNAs) were detected in 49% of cases with losses found in two or more cases affecting e.g. chromosome bands 3p13-p14.1 and 12p13. Furthermore, we identified two cases with a cryptic t(6;11) as well as several non-recurrent aberrations pointing to leukemia relevant regions. With regard to clinical outcome, there appeared to be an association between UPD 11p and UPD 13q cases with overall survival. These data demonstrate the potential of high-resolution SNP analysis for identifying genomic regions of potential pathogenic and clinical relevance in AML.
Project description:Comparison of copy number variations of acute myeloid leukemia mononuclear cells and the given cell types collected during complete remission of the acute myeloid leukemia
Project description:Unbalanced chromosomal abnormalities might play a major role in the leukemogenesis of AML-M5 Oligonucelotide array CGH were performed on 24 patients with AML-M5 To assess the possible existence of unbalanced chromosomal abnormalities and delineate the characterization of copy number alterations (CNAs) of acute myeloid leukemia-M5 (AML-M5)
Project description:Except for the well-known association with Down syndrome, there is little information on the genetic factors predisposing to acute myeloid leukemia. Germinal gene copy-number variations may represent risk factors for the disease. To identify copy number variants present in both normal and leukemic cells, we compared the Comparative Genomic Hybridization profiles of the blasts and healthy cells (CD3+ cells or peripheral lymphocytes during remission) of 13 patients (SET-A) and the blasts of a further 12 normal-karyotype acute myeloid leukemia patients (SET-B) for which only blasts DNA were available.
