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| Status |
Public on Jun 15, 2012 |
| Title |
Multilineage dysplasia does not influence prognosis in patients with CEBPA mutated AML supporting the WHO proposal to classify these patients as a unique entity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
By WHO 2008, CEBPA-mutated AML became a provisional subentity, but it remains to be clarified how CEBPAmut AML with multilineage dysplasia (MLD; ≥50% dysplastic cells in 2-3 lineages) but no other MDS-related feature should be classified. We investigated 108 CEBPAmut AML (15.7-87.6 years) for the impact of MLD and genetic features. MLD-positive patients differed from MLD-negative only by lower mean WBC counts (p=0.004), but not by other blood values, biologic characteristics, cytogenetic risk profiles, or additional molecular markers (NPM1mut, FLT3-ITD/TKD, RUNX1, MLL-PTD, IDH1/2). Biallelic CEBPAmut differed from wild-type-cases by differential expression of 213 genes, but did not differ significantly between MLD-positive/-negative patients. Survival outcomes were improved for females and those <60 years, intermediate versus adverse karyotypes (p=0.021), and for biallelic versus monoallelic/homozygous CEBPAmut (p=0.060) in case of FLT3-ITD-negativity. In contrast, 2-year OS (MLD+: 56.5%; MLD-: 65.5%) and 2-year EFS (MLD+: 13.8 months; MLD-: 16.3 months) did not differ significantly between MLD-positive/-negative patients. By univariable Cox regression analysis, gender, age, WBC count and MRC-cytogenetic risk category only were prognostically relevant for OS, while MLD was irrelevant. Therefore, CEBPAmut AML patients should be characterized only according to mut-status, cytogenetic risk groups, or additional mutations, whereas dysplasia is not relevant for this subtype.
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| Overall design |
The sample preparation assay for gene expression profiling using Affymetrix HG-U133 Plus 2.0 microarrays and subsequent data analysis were previously described. Only cases with biallelic CEBPA mutations were investigated by gene expression profiling due to previous reports that only double mutated cases conferred a specific gene expression signature, while monoallelic cases could not be discriminated from CEBPA wild-type cases. We performed comparison of gene expression profiles of 20 cases with biallelic CEBPA mutations and of 10 cases without CEBPA mutations.
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| Contributor(s) |
Bacher U, Schnittger S, Macijewski K, Grossmann V, Kohlmann A, Alpermann T, Kowarsch A, Kern W, Haferlach C, Haferlach T |
| Citation(s) |
22442349 |
| Submission date |
Oct 25, 2011 |
| 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 (30)
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| GSM822466 |
control MLL_00109 |
| GSM822467 |
control MLL_00116 |
| GSM822468 |
control MLL_00118 |
| GSM822469 |
control MLL_00107 |
| GSM822470 |
control MLL_00117 |
| GSM822471 |
control MLL_00110 |
| GSM822472 |
control MLL_00112 |
| GSM822473 |
MLD, biallelic AML MLL_00230 |
| GSM822474 |
MLD, biallelic AML MLL_00235 |
| GSM822475 |
MLD, biallelic AML MLL_00248 |
| GSM822476 |
MLD, biallelic AML MLL_00252 |
| GSM822477 |
MLD, biallelic AML MLL_00255 |
| GSM822478 |
MLD, biallelic AML MLL_00259 |
| GSM822479 |
MLD, biallelic AML MLL_00261 |
| GSM822480 |
MLD, biallelic AML MLL_00266 |
| GSM822481 |
MLD, biallelic AML MLL_00268 |
| GSM822482 |
no MLD, biallelic AML MLL_00233 |
| GSM822483 |
no MLD, biallelic AML MLL_00237 |
| GSM822484 |
no MLD, biallelic AML MLL_00239 |
| GSM822485 |
no MLD, biallelic AML MLL_00245 |
| GSM822486 |
no MLD, biallelic AML MLL_00257 |
| GSM822487 |
no MLD, biallelic AML MLL_00262 |
| GSM822488 |
no MLD, biallelic AML MLL_00263 |
| GSM822489 |
no MLD, biallelic AML MLL_00264 |
| GSM822490 |
no MLD, biallelic AML MLL_00265 |
| GSM822491 |
no MLD, biallelic AML MLL_00267 |
| GSM822492 |
no MLD, biallelic AML MLL_00269 |
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| Relations |
| BioProject |
PRJNA149157 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33223_RAW.tar |
136.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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