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Status |
Public on Apr 20, 2013 |
Title |
Acute myeloid leukemia with CEBPA double-mutations harbors in 76.8% of cases concomitant molecular mutations with TET2 and GATA2 alterations demonstrating strong prognostic impact |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Acute myeloid leukemia (AML) with CEBPA mutations is determined as provisional entity in the current WHO. A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon dm cases were shown to be associated with longer overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPAdm has not been assessed until now. Here, we investigated a cohort of 95 AML CEBPAdm cases for concomitant mutations. TET2 was found to be the most frequent mutation (32/94, 34.0%), followed by GATA2 (20/95, 21.0%), WT1 (13/95, 13.7%), DNMT3A (9/94, 9.6%), ASXL1 (9/95, 9.5%), NRAS (8/95, 8.4%), KRAS (3/94, 3.2%), IDH1/2 (6/95, 6.3%), FLT3-ITD (6/95, 6.3%), FLT3-TKD (2/95, 2.1%), NPM1 (2/95, 2.1%), and RUNX1 (1/94). No mutation was detected in MLL-PTD and TP53. With respect to prognostic impact, we observed that those cases harboring additional mutations in TET2 showed significant worse survival than wild-type cases (P=0.035), whereas GATA2 mutated cases showed improved survival (P=0.032). Further, using gene expression microarray analysis we identified no clear different clustering within the CEBPAdm cases with the distinct concomitant mutated genes. In conclusion, we demonstrated that 76.8% of CEBPAdm cases harbored additional alterations in other molecular markers and that CEBPA is a suitable MRD marker to control therapy.
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Overall design |
Total cohort contains 95 cases, but expression data available for 38 cases which were analyzed on Affymetrix HG-U133 Plus 2.0 arrays: 8 CEBPAdm and GATA2 mutated cases, 12 CEBPAdm and TET2 mutated cases, 7 CEBPAdm and ASXL1 mutated cases (n=3 showed an additional TET2 mutation) and 11 CEBPAdm without mutations in GATA2, TET2, and ASXL1.
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Contributor(s) |
Grossmann V, Haferlach C, Nadarajah N, Fasan A, Weissmann S, Roller A, Eder C, Stopp E, Kern W, Haferlach T, Kohlmann A, Schnittger S |
Citation(s) |
23521373 |
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Submission date |
Nov 06, 2012 |
Last update date |
Mar 25, 2019 |
Contact name |
Andreas Roller |
Organization name |
Munich Leukemia Laboratory
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Street address |
Max-Lebsche-Platz 31
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City |
Munich |
ZIP/Postal code |
81377 |
Country |
Germany |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (38)
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Relations |
BioProject |
PRJNA179072 |
Supplementary file |
Size |
Download |
File type/resource |
GSE42064_RAW.tar |
167.2 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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