Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct 13;12(10):2962.
doi: 10.3390/cancers12102962.

GATA2 Related Conditions and Predisposition to Pediatric Myelodysplastic Syndromes

Antonella Bruzzese  1 , Davide Leardini  2 , Riccardo Masetti  2 , Luisa Strocchio  1 , Katia Girardi  1 , Mattia Algeri  1 , Giada Del Baldo  1 , Franco Locatelli  1   3 , Angela Mastronuzzi  1
Affiliations
Review

GATA2 Related Conditions and Predisposition to Pediatric Myelodysplastic Syndromes

Antonella Bruzzese et al. Cancers (Basel). .

Abstract

Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for a transcriptional regulator of hematopoiesis. The genetic lesion as well as the clinical phenotype are extremely variable; many patients present hematological malignancies, especially MDS with the possibility to evolve into acute myeloid leukemia. Variable immune dysfunction, especially resulting in B- and NK-cell lymphopenia, lead to severe infections, including generalized warts and mycobacterial infection. Defects of alveolar macrophages lead to pulmonary alveolar proteinosis through inadequate clearance of surfactant proteins. Currently, there are no clear guidelines for the monitoring and treatment of patients with GATA2 mutations. In patients with MDS, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) that restores normal hematopoiesis preventing the progression to acute myeloid leukemia and clears long-standing infections. However, to date, the donor type, conditioning regimen, and the optimal time to proceed to HSCT, as well as the level of chimerism needed to reverse the phenotype, remain unclear highlighting the need for consensus guidelines.

Keywords: GATA2 deficiency; cancer predisposition; childhood MDS; myelodysplastic syndromes; pediatric cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
GATA2 gene and protein structure. GATA2 gene and protein structure. Mutations most frequently associated with MDS are circled [7]. TAD: transactivation domain, NRD: negative regulatory domain, ZF: zinc-finger domains, NLS: nuclear localization signal.
Figure 2
Figure 2
Possible algorithm for management of patients with GATA2 deficiency.
See this image and copyright information in PMC

References

    1. Cogle C.R., Craig B.M., Rollison D.E., List A.F. Incidence of the myelodysplastic syndromes using a novel claims-based algorithm: High number of uncaptured cases by cancer registries. Blood. 2011;117:7121–7125. doi: 10.1182/blood-2011-02-337964. - DOI - PMC - PubMed
    1. Locatelli F., Strahm B. How I Treat Myelodysplastic Syndromes of Childhood. Blood. 2018;131:1406–1414. doi: 10.1182/blood-2017-09-765214. - DOI - PubMed
    1. Hsu A.P., Sampaio E.P., Khan J., Calvo K.R., Lemieux J.E., Patel S.Y., Frucht D.M., Vinh D.C., Auth A.F., Freeman K.N., et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood. 2011;118:2653–2655. doi: 10.1182/blood-2011-05-356352. - DOI - PMC - PubMed
    1. Hahn C.N., Chong C.E., Carmichael C.L., Wilkins E.J., Brautigan P.J., Li X.C., Babic M., Lin M., Carmagnac A., Lee Y.K., et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat. Genet. 2011;43:1012. doi: 10.1038/ng.913. - DOI - PMC - PubMed
    1. Ostergaard P., Simpson M.A., Connell F.C., Steward C.G., Brice G., Woollard W.J., Dafou D., Kilo T., Smithson S., Lunt P., et al. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome) Nat. Genet. 2011;43:929–931. doi: 10.1038/ng.923. - DOI - PubMed