Transcriptomics

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Multilineage dysplasia does not influence prognosis in patients with CEBPA mutated AML supporting the WHO proposal to classify these patients as a unique entity


ABSTRACT: 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. 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: Tamara Alpermann  Andreas Kowarsch   Vera Grossmann   Claudia Haferlach   Alexander Kohlmann   Susanne Schnittger   Ulrike Bacher   Torsten Haferlach   Wolfgang Kern   Katja Macijewski    

PROVIDER: E-GEOD-33223 | ArrayExpress | 2012-06-14

SECONDARY ACCESSION(S): GSE33223PRJNA149157

REPOSITORIES: GEO, ArrayExpress

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Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity.

Bacher Ulrike U   Schnittger Susanne S   Macijewski Katja K   Grossmann Vera V   Kohlmann Alexander A   Alpermann Tamara T   Kowarsch Andreas A   Nadarajah Niroshan N   Kern Wolfgang W   Haferlach Claudia C   Haferlach Torsten T  

Blood 20120322 20


In 2008, the World Health Organization introduced CEBPA (encoding the CCAAT/enhancer binding protein)-mutated acute myeloid leukemia (AML) as a provisional entity. However, the classification of CEBPA-mutated AML with multilineage dysplasia (MLD; ≥ 50% dysplastic cells in 2-3 lineages) remains to be clarified. In the present study, we investigated 108 CEBPA-mutated AML patients for the impact of MLD, karyotype, and additional mutations. MLD(+) patients differed from MLD(-) patients only by lower  ...[more]

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