GRCh38 · COSMIC v94

Summary

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Reference
GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia.
Paper ID
COSP28918
Authors
Greif PA, Dufour A, Konstandin NP, Ksienzyk B, Zellmeier E, Tizazu B, Sturm J, Benthaus T, Herold T, Yaghmaie M, Dörge P, Hopfner KP, Hauser A, Graf A, Krebs S, Blum H, Kakadia PM, Schneider S, Hoster E, Schneider F, Stanulla M, Braess J, Sauerland MC, Berdel WE, Büchner T, Woermann BJ, Hiddemann W, Spiekermann K and Bohlander SK
Affiliation
Department of Internal Medicine 3, Ludwig-Maximilians-Universitaet (LMU), Munich, Germany;
Journal
Blood, 2012
ISSN: 1528-0020
PMID: 22649106 (view at PubMed or Europe PMC)
Abstract
Cytogenetically normal acute myeloid leukemia (CN-AML) with biallelic CEBPA gene mutations (biCEBPA) represents a distinct disease entity with a favorable clinical outcome. So far, it is not known if other genetic alterations cooperate with biCEBPA mutations during leukemogenesis. To identify additional mutations, we performed whole exome sequencing of five biCEBPA patients and detected somatic GATA2 zinc finger 1 (ZF1) mutations in 2 out of 5 cases. Both GATA2 and CEBPA are transcription factors crucial for hematopoietic development. Inherited or acquired mutations in both genes have been associated with leukemogenesis. Further mutational screening detected novel GATA2 ZF1 mutations in 13 of 33 biCEBPA positive CN-AML patients (13/33: 39.4%). No GATA2 mutations were found in 38 CN-AML patients with a monoallelic CEBPA mutation and in 89 CN-AML patients with wild-type CEBPA status. In reporter gene assays, all tested GATA2 ZF1 mutants showed reduced capacity to enhance CEBPA-mediated activation of transcription, suggesting that the GATA2 ZF1 mutations may collaborate with biCEPBA mutations to deregulate target genes during malignant transformation. We thus provide evidence for a genetically distinct subgroup of CN-AML. The AMLCG trials 1999 and 2008 are registered with the identifiers NCT00266136 and NCT01382147 at www.clinicaltrials.gov.
Paper Status
Curated