Details

Autor(en) / Beteiligte

• BULLINGER, L
• KRÖNKE, J
• DOWNING, J. R
• HOLZMANN, K
• DÖHNER, K
• DÖHNER, H
• SCHÖN, C
• RADTKE, I
• URLBAUER, K
• BOTZENHARDT, U
• GAIDZIK, V
• CARIO, A
• SENGER, C
• SCHLENK, R. F

Titel

Identification of acquired copy number alterations and uniparental disomies in cytogenetically normal acute myeloid leukemia using high-resolution single-nucleotide polymorphism analysis

Ist Teil von

• Leukemia, 2010-02, Vol.24 (2), p.438-449

Ort / Verlag

Avenel, NJ: Nature Publishing Group

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 UPDs were identified in 12% of cases and in the most frequently affected chromosomes, 6p, 11p and 13q. Notably, acquired UPD was invariably associated with mutations in nucleophosmin 1 (NPM1) or CCAAT/enhancer binding protein-alpha (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, for example, 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 seemed to be an association between UPD 11p and UPD 13q cases with overall survival. These data show the potential of high-resolution SNP analysis for identifying genomic regions of potential pathogenic and clinical relevance in AML.