B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells

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Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

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ŠEDA Václav MRÁZ Marek

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj European Journal of Haematology
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://onlinelibrary.wiley.com/doi/10.1111/ejh.12427/pdf
Doi http://dx.doi.org/10.1111/ejh.12427
Obor Onkologie a hematologie
Klíčová slova LYN; B cell; B-cell receptor; Bruton tyrosine kinase; Ibrutinib; MiRNA; PI(3)K; Spleen tyrosine kinase; ZAP-70
Přiložené soubory
Popis The physiology of B cells is intimately connected with the function of their B-cell receptor (BCR). B-cell lymphomas frequently (dys)regulate BCR signalling and thus take advantage of this pre-existing pathway for B-cell proliferation and survival. This has recently been underscored by clinical trials demonstrating that small molecules (fosfamatinib, ibrutinib, idelalisib) inhibiting BCR-associated kinases (SYK, BTK, PI3K) have an encouraging clinical effect. Here we describe the current knowledge of the specific aspects of BCR signalling in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukaemia (CLL) and normal B cells. Multiple factors can contribute to BCR pathway (dys)regulation in these malignancies and the activation of 'chronic' or 'tonic' BCR signalling. In lymphoma B cells, the balance of initiation, amplitude and duration of BCR activation can be influenced by a specific immunoglobulin structure, the expression and mutations of adaptor molecules (like GAB1, BLNK, GRB2, CARD11), the activity of kinases (like LYN, SYK, PI3K) or phosphatases (like SHIP-1, SHP-1 and PTEN) and levels of microRNAs. We also discuss the crosstalk of BCR with other signalling pathways (NF-KB, adhesion through integrins, migration and chemokine signalling) to emphasise that the 'BCR inhibitors' target multiple pathways interconnected with BCR, which might explain some of their clinical activity.
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