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

Blood. 2020 Feb 27;135(9):638-643. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism*
  • Humans
  • 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