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: Emberger syndrome; GATA2; MonoMAC syndrome; immunodeficiency; pulmonary alveolar proteinosis.