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CEBPA double‐mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76·8% of cases with TET 2 and GATA 2 alterations impacting prognosis
Author(s) -
Grossmann Vera,
Haferlach Claudia,
Nadarajah Niroshan,
Fasan Annette,
Weissmann Sandra,
Roller Andreas,
Eder Christiane,
Stopp Elisa,
Kern Wolfgang,
Haferlach Torsten,
Kohlmann Alexander,
Schnittger Susanne
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12297
Subject(s) - cebpa , myeloid leukaemia , mutation , myeloid , concomitant , microbiology and biotechnology , biology , gene , chemistry , genetics , medicine , immunology
Summary Acute myeloid leukaemia ( AML ) with CEBPA 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 CEBPA dm cases were shown to be associated with better overall survival ( OS ). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPA dm has not been assessed until now with exception of GATA 2 mutations. Here, we investigated a cohort of 95 AML CEBPA dm cases for concomitant mutations. TET 2 was found to be most frequently mutated (34·0%) gene, followed by GATA 2 (21·0%), WT 1 (13·7%), DNMT 3A (9·6%), ASXL 1 (9·5%), NRAS (8·4%), KRAS (3·2%), IDH 1/2 (6·3%), FLT 3 ‐internal tandem duplication (6·3%), FLT 3 ‐tyrosine kinase domain (2·1%), NPM 1 (2·1%), and RUNX 1 (1/94). Patients harbouring additional mutations in the TET 2 gene showed significantly worse OS than TET 2 wild‐type cases ( P = 0·035), whereas GATA 2 ‐mutated patients showed improved OS ( P = 0·032). Serial analyses were performed for 39 CEBPA dm cases with concomitant mutations. Here, we observed that CEBPA mutations present the primary pathogenetic event in the majority of cases (76·9%). Further, a distinct gene expression profile ( GEP ) was confirmed for CEBPA dm versus CEBPA sm or CEBPA wild‐type cases while no significant changes in GEP were observed related to additional mutations within the CEBPA dm AML .