ETV6-related thrombocytopenia and leukemia predisposition

Abstract

Germ line mutations in ETV6 are responsible for a familial thrombocytopenia and leukemia predisposition syndrome. Thrombocytopenia is almost completely penetrant and is usually mild. Leukemia is reported in ∼30% of carriers and is most often B-cell acute lymphoblastic leukemia. The mechanisms by which ETV6 dysfunction promotes thrombocytopenia and leukemia remain unclear. Care for individuals with ETV6-related thrombocytopenia and leukemia predisposition includes genetic counseling, treatment or prevention of excessive bleeding and surveillance for the development of hematologic malignancy.

Graphical abstract

Figure 1.

Abnormal bone marrow histology and CBCs in patients with ETV6-related thrombocytopenia and leukemia predisposition. (A) Abnormal cellular features (yellow arrows) with hyperchromatic small megakaryocytes, disseminated toxic granulations, and dysplastic eosinophils (magnification ×100; Wright-Giemsa stain). (B) Platelet count, white blood cell (WBC) count, hemoglobin (Hgb), mean cell volume (MCV), and mean platelet volume (MPV) in patients (PT) with germ line mutations in ETV6, as compared with related individuals (Rel) without mutation (Student t test).^-,,

Figure 2.

Schematic of ETV6 protein with functional domains and location of germ line mutations from 23 reported pedigrees. The number of families with alterations at the site is indicated in the circles if >1. A deletion that includes all of exon 2 has also been reported. *Germ line deletions in ETV6 involving splice sites.