The different faces of GATA2 deficiency: implications for therapy and surveillance

Luca Vinci; Brigitte Strahm; Carsten Speckmann; Miriam Erlacher

doi:10.3389/fonc.2024.1423856

The different faces of GATA2 deficiency: implications for therapy and surveillance

Front Oncol. 2024 Jun 27:14:1423856. doi: 10.3389/fonc.2024.1423856. eCollection 2024.

Authors

Luca Vinci¹, Brigitte Strahm¹, Carsten Speckmann^{1

2}, Miriam Erlacher^{1

3}

Affiliations

¹ Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.

Abstract

GATA2 deficiency is one of the most common genetic predispositions to pediatric myelodysplastic syndrome (MDS) in children and adolescents. The wide spectrum of disease comprises, among others, hematological, immunological and pulmonary manifestations, as well as occasionally distinct organ anomalies. Due to the elevated risk of progression, nearly all individuals with GATA2-related MDS eventually undergo a hematopoietic stem cell transplantation (HSCT) at some point in their lives. Nevertheless, the optimal timing, method, and even the indication for HSCT in certain cases are still matter of debate and warrant further research. In this article, we report five patients with different hematological and immunological manifestations of GATA2 deficiency ranging from immunodeficiency and refractory cytopenia of childhood without chromosomal aberrations to relapsed MDS-related acute myeloid leukemia. We discuss the adopted strategies, including intensity of surveillance, indication and timing of HSCT, based on morphological, clinical and molecular markers, as well as individual patient needs. We conclude that a better characterization of the natural disease course, a better understanding of the prognostic significance of somatic aberrations and a thorough evaluation of patients´ perspectives and preferences are required to achieve a personalized approach aimed at improving the care of these patients.

Keywords: Cancer predisposition; GATA2; HSCT; mds; myeloid neoplasia.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was generated within the European Reference Network for Paediatric Cancer (PAEDCAN) and the European Reference Network on Rare Hematological Diseases (EuroBloodNet). The authors acknowledge the contribution of the Center of Inherited and Acquired Blood Diseases at the Freiburg Center for Rare Diseases, and the Hilda Biobank at the Department of Pediatrics and Adolescent Medicine, Freiburg, Germany. This work was in part supported by the German Federal Ministry of Education and Research (BMBF) 01GM1911A and 01GM2207A “MyPred -Network for young individuals with syndromes predisposing to myeloid malignancies” (to ME and BS), “Deutsche José Carreras Leukämie-Stiftung” (DJCLS 13R/2022 to ME) and EJP-RD Project “3D-GATA2” to ME. We also acknowledge support by the Open Access Publication Fund of the University of Freiburg.