CEBPA double‐mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76·8% of cases with TET2 and GATA2 alterations impacting prognosis. (25th March 2013)

• Record Type: Journal Article
• Authors: Grossmann, Vera; Haferlach, Claudia; Nadarajah, Niroshan; Fasan, Annette; Weissmann, Sandra; Roller, Andreas; Eder, Christiane; Stopp, Elisa; Kern, Wolfgang; Haferlach, Torsten; Kohlmann, Alexander; Schnittger, Susanne
• Is Part Of: British journal of haematology. Volume 161:Number 5(2013:Jun.)
• Page Start: 649
• Page End: 658
• Publication Date: 2013-03-25
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12297
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12297-abs-0001"> <title>Summary</title> <p>Acute myeloid leukaemia (AML) with <italic>CEBPA</italic> mutations is listed as a provisional entity in the current World Health Organization classification. A difference in clinical outcome between single‐ (sm) and double‐mutated (dm) cases has been reported, whereupon <italic>CEBPA</italic>dm cases were shown to be associated with better overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to <italic>CEBPA</italic>dm has not been assessed until now with exception of <italic>GATA2</italic> mutations. Here, we investigated a cohort of 95 AML <italic>CEBPA</italic>dm cases for concomitant mutations. <italic>TET2</italic> was found to be most frequently mutated (34·0%) gene, followed by <italic>GATA2</italic> (21·0%), <italic>WT1</italic> (13·7%), <italic>DNMT3A</italic> (9·6%), <italic>ASXL1</italic> (9·5%), <italic>NRAS</italic> (8·4%), <italic>KRAS</italic> (3·2%), <italic>IDH1/2</italic> (6·3%), <italic>FLT3</italic>‐internal tandem duplication (6·3%), <italic>FLT3</italic>‐tyrosine kinase domain (2·1%), <italic>NPM1</italic> (2·1%), and <italic>RUNX1</italic> (1/94). Patients harbouring additional mutations in the <italic>TET2</italic> gene showed significantly worse OS than <italic>TET2</italic> wild‐type cases (<italic>P </italic>=<italic> </italic>0·035), whereas <italic>GATA2</italic>‐mutated patients showed improved OS (<italic>P </italic>=<italic> </italic>0·032). Serial analyses were performed for 39 <italic>CEBPA</italic>dm cases with concomitant mutations. Here, we observed that <italic>CEBPA</italic> mutations present the primary pathogenetic event in the majority of cases (76·9%). Further, a distinct gene expression profile (GEP) was confirmed for <italic>CEBPA</italic>dm <italic>versus CEBPA</italic>sm or <italic>CEBPA</italic> wild‐type cases while no significant changes in GEP were observed related to additional mutations within the <italic>CEBPA</italic>dm AML.</p> </abstract>