Myeloid malignancies with somatic GATA2 mutations can be associated with an immunodeficiency phenotype

Abstract

Germline mutations in GATA2 are associated with a complex immunodeficiency and cancer predisposition syndrome. Somatic GATA2^mut in myeloid malignancies may impart a similar phenotype. We reviewed adult patients with a diagnosis of GATA2^mut hematological malignancy who were referred to our HHMC for genetic testing, and identified to have somatic GATA2^mut. Nine patients with a median age of 63 years were included. Six patients (66.7%) were males. Atypical CML and acute myeloid leukemia were the most common initial presentation. The median overall VAF was 47.14%. Monocytopenia was pronounced when the GATA2^mut involved the C-terminal ZFD. GATA2 N-terminal ZFD mutations tend to be co-mutated with biCEBPA^mut. Unlike germline GATA2 mutations, monocytopenia associated with somatic GATA2 mutations often resolved at remission. We concluded that similar to germline GATA2 mutations, a subset of somatic GATA2 mutations can impart a germline phenotype.

Keywords:

• GATA2
• immunodeficiency
• MonoMAC syndrome
• Emberger syndrome
• pulmonary alveolar proteinosis

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http:\\10.1080/10428194.2018.1551535.

Additional information

Funding

This work was supported in part by the MD Anderson Cancer Centre Support Grant (CCSG) [CA016672]. The MD Anderson Cancer Center Leukemia SPORE [CA100632]. The Charif Souki Cancer Research Fund and generous philanthropic contributions to the MD Anderson Moon Shots Program. NIH-NIAID [R01AI120989] (J.S.O.) and an American Society for Hematology Junior Scholar Award (E.M.M.).