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@article{1216835, author = {Šeda, Václav and Mráz, Marek}, article_location = {Hoboken (USA)}, article_number = {3}, doi = {http://dx.doi.org/10.1111/ejh.12427}, keywords = {LYN; B cell; B-cell receptor; Bruton tyrosine kinase; Ibrutinib; MiRNA; PI(3)K; Spleen tyrosine kinase; ZAP-70}, language = {eng}, issn = {0902-4441}, journal = {European Journal of Haematology}, title = {B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells}, url = {http://onlinelibrary.wiley.com/doi/10.1111/ejh.12427/pdf}, volume = {94}, year = {2015} }
TY - JOUR ID - 1216835 AU - Šeda, Václav - Mráz, Marek PY - 2015 TI - B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells JF - European Journal of Haematology VL - 94 IS - 3 SP - 193-205 EP - 193-205 PB - Wiley-Blackwell SN - 09024441 KW - LYN KW - B cell KW - B-cell receptor KW - Bruton tyrosine kinase KW - Ibrutinib KW - MiRNA KW - PI(3)K KW - Spleen tyrosine kinase KW - ZAP-70 UR - http://onlinelibrary.wiley.com/doi/10.1111/ejh.12427/pdf L2 - http://onlinelibrary.wiley.com/doi/10.1111/ejh.12427/pdf N2 - 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. ER -
ŠEDA, Václav a Marek MRÁZ. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. \textit{European Journal of Haematology}. Hoboken (USA): Wiley-Blackwell, 2015, roč.~94, č.~3, s.~193-205. ISSN~0902-4441. Dostupné z: https://dx.doi.org/10.1111/ejh.12427.
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