Classification of CEBPA mutated acute myeloid leukemia by GATA2 mutations

Classification of CEBPA mutated acute myeloid leukemia by GATA2 mutationsTo the editor: Acute myeloid leukemia (AML) with mutated CCAAT/enhancer binding protein a (CEBPA) is listed as a provisional subtype by the World Health Organization.AML with CEBPA mutations are classified into the favorable risk group due to their high remission and survival rates.CEBPA mutations are found in ;10% of AML [1] with two main hotspots i.e., N-terminal out-of-frame mutations abolish translation of the full-length isoform and C-terminal mutations of the basic leucine zipper domain disrupting DNA binding or dimerization [2].The majority of mutations are bi-allelic or double, however, homozygous mutations have been described [3,4].The GATA2 gene encodes a transcription factor involved in normal hematopoiesis.Recent studies associated GATA2 mutations with CEBPA double mutations and improved overall survival (OS) [5,6].In contrast, another study failed to show any impact thereof on OS [1].In this study, we investigate the prognostic significance of GATA2 mutations in a cohort of 128 patients with CEBPA-mutated AML.Diagnostic bone marrow samples of 128 patients with CEBPA mutated AML were analyzed.Patients were enrolled between 1999 and 2012 and included in the clinical trials of the ALFA group 9801, 9802, 9803, 0701, and 0702 (ClinicalTrials.govIDs: NCT 00931138, 00880243, 00363025, 00927498, 00932412).Children were enrolled on the ELAM02 trial (ClinicalTrials.govID: NCT 00149162).Studies were approved by the local Institutional Review Boards and conducted after informed consent was obtained in accordance with the Declaration of Helsinki.All patients were treated with intensive chemotherapy.Genomic DNA was analyzed for the entire coding region of CEBPA, WT1 (exon 7 and 9), and NPM1 (exon 12) using PCR and direct Sanger sequencing.FLT3 internal tandem duplications (FLT3-ITD) were detected by PCR and fragment analysis [7].We sequenced GATA2 (exons 4-6, aa291 to 466) according to Greif et al. [8].Additionally, high-quality RNA of 70 CEBPA mutated AML patients was available for gene expression analysis using Affymetrix HG U133 Plus 2.0 microarrays (Santa Clara, USA).Cumulative incidence of relapse (CIR) and OS were estimated by the Kaplan-Meier method after stratification by trials.Death in first complete remission (CR) was taken