Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
Publ. Version/Full Text
DOI
PMC
 |
Free by publisher |
as soon as is submitted to ZB.
Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome.
J. Clin. Oncol. 28, 570-577 (2010)
Purpose CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal (CN) acute myeloid leukemia (AML). Patients and Methods: Four hundred sixty-seven homogeneously treated patients with CN-AML were subdivided into moCEBPA, biCEBPA, and wild-type (wt) CEBPA patients. The subgroups were analyzed for clinical parameters and for additional mutations in the NPM1, FLT3, and MLL genes. Furthermore, we obtained gene expression profiles using oligonucleotide microarrays. Results: Only patients with biCEBPA had an improved median overall survival when compared with patients with wtCEBPA (not reached v 20.4 months, respectively; P = .018), whereas patients with moCEBPA (20.9 months) and wtCEBPA had a similar outcome (P = .506). Multivariable analysis confirmed biCEBPA, but not moCEBPA, mutations as an independent favorable prognostic factor. Interestingly, biCEBPA mutations, compared with wtCEBPA, were never associated with mutated NPM1 (0% v 43%, respectively; P < .001) and rarely associated with FLT3 internal tandem duplication (ITD; 5% v 23%, respectively; P = .059), whereas patients with moCEBPA had a similar frequency of mutated NPM1 and a significantly higher association with FLT3-ITD compared with patients with wtCEBPA (44% v 23%, respectively; P = .037). Furthermore, patients with biCEBPA showed a homogeneous gene expression profile that was characterized by downregulation of HOX genes, whereas patients with moCEBPA showed greater heterogeneity in their gene expression profiles. Conclusion: Biallelic disruption of the N and C terminus of CEBPA is required for the favorable clinical outcome of CEBPA-mutated patients and represents a distinct molecular subtype of CN-AML with a different frequency of associated gene mutations. These findings are of great significance for risk-adapted therapeutic strategies in AML.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
MINIMAL RESIDUAL DISEASE; BINDING-PROTEIN-ALPHA; C/EBP-ALPHA; PROGNOSTIC-SIGNIFICANCE; EXPRESSION PROFILE; TANDEM DUPLICATION; RELAPSE SAMPLES; AML; FLT3; CYTOGENETICS
ISSN (print) / ISBN
0732-183X
e-ISSN
1527-7755
Quellenangaben
Volume: 28,
Issue: 4,
Pages: 570-577
Publisher
American Society of Clinical Oncology
Publishing Place
Alexandria
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)