Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Herold, T; Metzeler, KH; Vosberg, S; Hartmann, L; Röllig, C; Stölzel, F; Schneider, S; Hubmann, M; Zellmeier, E; Ksienzyk, B; Jurinovic, V; Pasalic, Z; Kakadia, PM; Dufour, A; Graf, A; Krebs, S; Blum, H; Sauerland, MC; Büchner, T; Berdel, WE; Woermann, BJ; Bornhäuser, M; Ehninger, G; Mansmann, U; Hiddemann, W; Bohlander, SK; Spiekermann, K; Greif, PA.
Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis.
Blood. 2014; 124(8): 1304-1311.
Doi: 10.1182/blood-2013-12-540716
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Vosberg Sebastian
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- Abstract:
- In acute myeloid leukemia (AML), isolated trisomy 13 (AML+13) is a rare chromosomal abnormality whose prognostic relevance is poorly characterized. We analyzed the clinical course of 34 AML+13 patients enrolled in the German AMLCG-1999 and SAL trials and performed exome sequencing, targeted candidate gene sequencing and gene expression profiling. Relapse-free (RFS) and overall survival (OS) of AML+13 patients were inferior compared to other ELN Intermediate-II patients (n=855) (median RFS, 7.8 vs 14.1 months, P = .006; median OS 9.3 vs. 14.8 months, P = .004). Besides the known high frequency of RUNX1 mutations (75%), we identified mutations in spliceosome components in 88%, including SRSF2 codon 95 mutations in 81%. Recurring mutations were detected in ASXL1 (44%) and BCOR (25%). Two patients carried mutations in CEBPZ, suggesting that CEBPZ is a novel recurrently mutated gene in AML. Gene expression analysis revealed a homogeneous expression profile including upregulation of FOXO1 and FLT3 and downregulation of SPRY2. This is the most comprehensive clinical and biological characterization of AML+13 to date, and reveals a striking clustering of lesions in a few genes, defining AML+13 as a genetically homogeneous subgroup with alterations in a few critical cellular pathways. Clinicaltrials.gov identifiers: AMLCG-1999: NCT00266136; AML96: NCT00180115; AML2003: NCT00180102; and AML60+: NCT00893373. © 2014 by The American Society of Hematology.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Aged, 80 and over -
- Chromosomes, Human, Pair 13 - genetics
- Chromosomes, Human, Pair 13 - metabolism
- Disease-Free Survival -
- Female -
- Gene Expression Regulation, Leukemic - genetics
- Gene Expression Regulation, Leukemic - epidemiology
- Humans -
- Leukemia, Myeloid, Acute - genetics
- Leukemia, Myeloid, Acute - metabolism
- Leukemia, Myeloid, Acute - mortality
- Leukemia, Myeloid, Acute - pathology
- Male -
- Middle Aged -
- Neoplasm Proteins - biosynthesis
- Neoplasm Proteins - genetics
- Survival Rate -
- Trisomy - genetics
- Trisomy - pathology
- Up-Regulation - genetics