Increased activation of PI3 kinase-δ predisposes to B-cell lymphoma

• Published in: Blood 2020-02, Vol.135 (9), p.638-643
• Main Authors: Durandy, Anne, Kracker, Sven
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cancer; Cell Transformation, Neoplastic - immunology; Cell Transformation, Neoplastic - metabolism; Humans; Immunology; Life Sciences; Lymphoma, B-Cell - etiology; Phosphatidylinositol 3-Kinases - metabolism; Primary Immunodeficiency Diseases - complications; Primary Immunodeficiency Diseases - immunology; Primary Immunodeficiency Diseases - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2019002072

Activated phosphatidylinositol 3-kinase-δ (PI3K-δ) syndrome (APDS) is a rare primary combined immunodeficiency caused by either dominant gain-of-function mutations in the PIK3CD gene encoding the catalytic subunit p110δ of PI3K-δ (referred to as type 1 APDS) or dominant loss-of-function mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits (type 2 APDS). In types 1 and 2 APDS, the PI3K-δ hyperactivity resulting from the gene mutations leads to similar clinical presentations, characterized by increased susceptibility to bacterial and viral infections and (to a lesser extent) autoimmune manifestations. A hallmark of this disease is lymphoproliferation, which may even be life threatening and require repeated surgical treatment. A major complication of APDS is malignancy (especially B-cell lymphomas), which greatly worsens the prognosis. Here, we review the different neoplastic conditions observed in patients with APDS and discuss the uncontrolled PI3K-δ activity in B and T cells that leads to malignant transformation. [Display omitted]