Can somatic GATA2 mutation mimic germ line GATA2 mutation?

M Sekhar, R Pocock, D Lowe, C Mitchell, T Marafioti… - Blood Advances, 2018 - Elsevier
M Sekhar, R Pocock, D Lowe, C Mitchell, T Marafioti, R Dickinson, M Collin, M Lipman
Blood Advances, 2018Elsevier
GATA2 is a zinc-finger transcription factor integral to hemopoietic stem cell regulation,
mononuclear development, and alveolar macrophage activity. 1 Heterozygous germ line
GATA2 mutations are associated with mycobacterial infection, monocytopenia, and
deficiency of B/natural killer cells, and pulmonary alveolar proteinosis (PAP). GATA2
mutations confer a 90% lifetime risk of developing myelodysplastic syndrome (MDS)/acute
myeloid leukemia (AML) with mutations detected in 7% to 15% of MDS in young adults and …
GATA2 is a zinc-finger transcription factor integral to hemopoietic stem cell regulation, mononuclear development, and alveolar macrophage activity. 1 Heterozygous germ line GATA2 mutations are associated with mycobacterial infection, monocytopenia, and deficiency of B/natural killer cells, and pulmonary alveolar proteinosis (PAP). GATA2 mutations confer a 90% lifetime risk of developing myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) with mutations detected in 7% to 15% of MDS in young adults and children. 2, 3 GATA2 mutations can be present in germ line or arise somatically, and, in either case, heterozygous mutations can prove clinically consequential. The clinical features of GATA2 mutation are largely known through studies of germ line mutation, which may be inherited or arise de novo. 2, 3, 4, 5, 6 Somatic mutations have been reported as drivers of myeloid neoplasia, including myeloproliferative neoplasms (MPN), and are well described in leukemia arising in the context of bi-allelic CEBPA mutation. 7 However, features such as mononuclear cytopenia, immunodeficiency, and pulmonary alveolar proteinosis (PAP) have not been reported.
PAP is a rare syndrome characterized by the abnormal accumulation of surfactant in the alveoli and terminal airways resulting in respiratory failure. 8 Neutralizing anti–granulocyte macrophage colony-stimulating factor (anti–GM-CSF) antibodies are detected in the majority of patients with primary PAP. Secondary PAP (sPAP), which is associated with hematologic malignancies (chiefly MDS/AML), results from intrinsic dysregulation of alveolar macrophages. 9, 10 Median survival is< 50% at 2 years, and mortality is mainly due to PAP itself. Twenty-five percent of sPAP patients have germ line GATA2 mutations, and one-fifth of germ line GATA2-mutated individuals develop PAP. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10
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