Acute myeloid leukemia (AML) represents a heterogeneous group of hematological neoplasms associated with the accumulation of acquired genetic and epigenetic aberrations in hematopoietic progenitor cells. Myeloid leukemogenesis is directly linked to the disruption of expression of transcription factors that regulate the proliferation, survival and differentiation of myeloid progenitors. Moreover, overexpression of particular genes has been associated with prognosis in AML, enabling patients with different survival rates to be identified within cytogenetic risk groups. The GATA2 gene encodes a transcription factor that mediates essential functions in hematopoietic stem cell and progenitor cell (HSC/HPC) compartments. The essential role of GATA2 in hematopoiesis is evident in mice lacking GATA2, which are anemic, have fewer HSC/HPC cells and that die by day 10–11 of gestation. 1 Expression of GATA2 is critical at various stages of hematopoiesis, and as it in part determines the fate of distinct myeloid lineages, GATA2 expression is tightly regulated. Indeed, ectopic expression of GATA2 has been reported to promote erythroblast proliferation while blocking terminal erythroid differentiation. 2 Furthermore, alterations in GATA2 expression have been observed in patients with myelodysplastic syndrome, where it has been related to severe dysplasia. 3 Nevertheless, to date, only two studies have analyzed the expression of GATA2 in AML. Strong GATA2 expression was found in 87% of AML patients (54/62) using single-round RT-PCR. 4 More recently, Ayala et al. 5 analyzed the expression of GATA2 in 41 patients with AML by real-time quantitative RT-PCR (QRT-PCR). They found that 21 cases had expression of GATA2 (52%), and defined overexpression as the expression values that were over the median value in GATA2-expressing patients. Therefore, to further clarify the significance of GATA2 overexpression in AML, we investigated its prevalence in a large series of AML patients using QRT-PCR. Furthermore, using an established cutoff value, we correlated these results with cytogenetic data and molecular markers, and we determined the prognostic relevance of GATA2 expression levels. GATA2 expression was analyzed in bone marrow samples from 259 AML patients referred for analysis to the University of Navarra (Spain). Gene expression was quantified using the ABI Prism 7500 Real Time PCR System and TaqMan Gene Expression Assays (Applied Biosystems, Foster City, CA, USA), with GAPDH as an internal control. A gene was considered to be overexpressed if its expression level was greater than the established cutoff value determined for each gene (mean±3 sd), defined by the analysis of 10 bone marrow samples from normal donors. Statistical analyses were performed using the SPSS software package (v. 15, SPSS Inc., Chicago, IL, USA). More detailed information about the molecular and statistical analyses performed is provided in the Supplementary Information.

Using the calculated cutoff value for GATA2 expression, we divided patients into two groups:‘cases with overexpression of GATA2’and ‘cases with no GATA2 overexpression’. With this approach, we found that GATA2 was overexpressed in 37.4% of cases (97/259), suggesting that this could be a recurrent event in AML (Table 1 and Supplementary Figure 1). Thus, for the first