GATA2 Mutations Predict Poor Prognosis in Transplanted Myeloid Neoplasms.

BACKGROUND

GATA binding protein 2 (GATA2) plays a crucial role in the differentiation, proliferation, and maintenance of hematopoietic stem cells (HSCs). GATA2 mutations have been identified in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), but the impact of somatic GATA2 mutations on prognosis remains controversial, especially on patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT).

OBJECTIVES

The aim of this retrospective case-control study was to explore the prognostic significance of somatic GATA2 mutations in MDS/AML patients who underwent allo-HSCT.

STUDY

DESIGN

Propensity score matching (PSM) analysis was used to match patients with wild-type GATA2 as the control group (ratio 1:3). A total of 14 patients with somatic GATA2 mutations and 39 patients with wild-type GATA2 were enrolled.

RESULTS

The baseline characteristics were comparable between the two groups. However, patients with GATA2 mutations had a higher frequency of WT1 mutations and relapse rate (p = 0.036 and p = 0.008, respectively). Compared to patients with wild-type GATA2, patients with GATA2 mutations had shorter progression-free survival (PFS) and overall survival (OS), and post-transplant PFS (p < 0.001, p = 0.030, and p = 0.004, respectively). Subgroup analysis showed that the PFS, OS, post-transplant PFS, and OS of patients with GATA2 non-zinc finger domain 1 (non-ZF1) mutations (p < 0.001, p = 0.004, p < 0.001, and p = 0.049, respectively), but not those of patients with somatic GATA2 ZF1 mutations, were shorter than that of patients with wild-type GATA2. Moreover, somatic GATA2 mutations and WBC count ≥ 20.86 × 109/L were independent adverse prognostic factors for PFS (p = 0.005 and p = 0.020, respectively). Relapse before transplantation was an independent adverse prognostic factor for OS (p = 0.009).

CONCLUSIONS

Our preliminary study revealed that somatic GATA2 mutations, especially non-ZF1 mutations, may be associated with unfavorable outcomes in patients with MDS/AML, even for patients who underwent allo-HSCT.