GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations

Abstract

GATA2 mutations have recently been reported in acute myeloid leukaemia (AML) patients with CEBPA-double mutations. To explore their impact on this favourable-risk disease, we determined GATA2 status in 153 sporadic AML patients and three members of a germ-line CEBPA-mutant family at AML presentation. Overall, 27% (15/55) CEBPA-double, 16% (7/43) CEBPA-single and 0% (0/55) normal karyotype/CEBPA-wild-type patients were GATA2-mutant. All familial AML patients acquired both a second CEBPA and a GATA2 mutation. CEBPA and GATA2 mutant levels indicated that both mutations were likely to be early events in leukaemogenesis. GATA2 status did not impact on the favourable outcome of CEBPA-double/FLT3-inernal tandem duplication-negative patients.

Classification of CEBPA mutated acute myeloid leukemia by GATA2 mutations

“…We confirmed that GATA2 mutations were significantly associated with CEBPA dm cases (29%, 4 of 41 sm vs. 25 of 87 dm: Fisher's exact test P 5 0.022). In contrast to previous reports [5,8], we have detected GATA2 mutations in CEBPA sm cases at a small frequency of 4% as has Green et al [9] (Table 2).…”

“…They were specifically associated with CEBPA sm cases (12 of 40 sm vs. 0 of 78 dm, P < 0.0001) and mutually exclusive of GATA2 mutations (12 of 93 GATA2 wild-type vs. 0 of 25 GATA2 mutated, P < 0.0001). Previous reports found no co-occurrence of FLT3-ITD with GATA2 mutations [5,9]. In contrast to our finding using a larger cohort of CEBPA mutated patients, we have detected three GATA2 mutated cases within 10 FLT3-ITD positive patients (30%).…”

“…However, we confirmed no prognostic impact of GATA2 mutations (n 5 25) compared to wild-type (n 5 62) in our cohort of CEBPA dm AML [8,9] (22 vs. 58 and 10 vs. 16) with a trend similar of better outcome in CEBPA dm with GATA2 mutations compared to wild-type [5,6] (18 vs. 62). Furthermore, our study provided first evidence that homozygous CEPBA mutations have a similar gene expression signature as CEPBA dm and thus may be considered as equivalent.…”

“…Many ITP patients, particularly patients with anti-GP Ib-IX autoantibodies, do not respond to conventional treatments such as steroids, intravenous immunoglobulins, or splenectomy [4][5][6][7][8]. Also the role of new therapies like thrombopoietin agonist are unclear and not without risks [9]. Oseltamivir phosphate, the ethyl ester prodrug of oseltamivir carboxylate that conventionally serves as an antiviral sialidase inhibitor, has been prescribed worldwide for the treatment of patients with influenza [10].…”

Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors

“…13,14 Gene expression studies have shown that CEBPA bi samples, but not specimens with CEBPA monoallelic mutations, have a distinctive gene expression profile (GEP), [15][16][17][18] and analyses of small series indicated a possibility that this profile is shared by some atypical CEBPA bi AML. 15 Mutations in genes such as GATA2, WT1, and TET2 have been described thus far in CEBPA bi specimens, [19][20][21][22] including 6 specimens reported in The Cancer Genome Atlas cohort. 7 We previously used comparative transcriptomic approaches to report the mutational and transcriptional landscapes of MLL,…”