PI3K Signaling in Normal B Cells and Chronic Lymphocytic Leukemia (CLL)

Current Topics in Microbiology and Immunology
Klaus Okkenhaug, Jan A Burger

Abstract

B cells provide immunity to extracellular pathogens by secreting a diverse repertoire of antibodies with high affinity and specificity for exposed antigens. The B cell receptor (BCR) is a transmembrane antibody, which facilitates the clonal selection of B cells producing secreted antibodies of the same specificity. The diverse antibody repertoire is generated by V(D)J recombination of heavy and light chain genes, whereas affinity maturation is mediated by activation-induced cytidine deaminase (AID)-mediated mutagenesis. These processes, which are essential for the generation of adaptive humoral immunity, also render B cells susceptible to chromosomal rearrangements and point mutations that in some cases lead to cancer. In this chapter, we will review the central role of PI3K s in mediating signals from the B cell receptor that not only facilitate the development of functional B cell repertoire, but also support the growth and survival of neoplastic B cells, focusing on chronic lymphocytic leukemia (CLL) B cells. Perhaps because of the central role played by PI3K in BCR signaling, B cell leukemia and lymphomas are the first diseases for which a PI3K inhibitor has been approved for clinical use.

Citations

Dec 15, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Bart VanhaesebroeckRoberto Piñeiro
Sep 15, 2020·Exploration of Targeted Anti-tumor Therapy·Joe TaylorGraham Packham
Jan 24, 2019·International Journal of Molecular Sciences·Vanessa Edna SanchezYong-Mi Kim
Apr 4, 2021·Cancers·Valerio Guarente, Paolo Sportoletti
Dec 26, 2018·Journal of Medicinal Chemistry·Matthew W D PerryAnnika Westin Eriksson
Aug 24, 2021·Frontiers in Immunology·Kristoffer H JohansenKlaus Okkenhaug

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Methods Mentioned

BETA
transgenic
GTPases

Clinical Trials Mentioned

NCT01539512
NCT02004522
NCT01578707
NCT01282424
NCT01882803
NCT01499303
NCT01799889
NCT01796470

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