Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab 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 FullText FullText_MUG

Co-authors Med Uni Graz: Vosberg Sebastian
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
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