Premium
MYC protein dysregulation is driven by BCR ‐ PI 3K signalling in diffuse large B‐cell lymphoma
Author(s) -
Wang WeiGe,
Liu ZeBing,
Jiang XiangNan,
Lee Jimmy,
Zhou XiaoYan,
Li XiaoQiu
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13287
Subject(s) - breakpoint cluster region , cancer research , pi3k/akt/mtor pathway , phosphorylation , b cell receptor , biology , protein kinase b , signal transduction , b cell , microbiology and biotechnology , immunology , receptor , antibody , genetics
Aims MYC overexpression is a common feature of diffuse large B‐cell lymphoma ( DLBCL ) and is associated with poor prognosis in patients with this neoplasm. We aimed to investigate the underlying mechanisms of MYC dysregulation, as they have not been fully determined. Methods and results We immunohistochemically evaluated the correlation between B‐cell receptor ( BCR )–phosphoinositide 3‐kinase ( PI 3K) pathway activity and MYC level in 108 cases of de‐novo DLBCL , 25 of which featured loss of BCR , and investigated the effects of BCR – PI 3K signalling on MYC level and phosphorylation in DLBCL cell lines. The expression levels of phospho‐ SYK and phospho‐ AKT correlated with MYC expression in BCR ‐positive DLBCL . MYC expression was significantly lower in BCR ‐negative tumour tissues than in BCR ‐positive tumour tissues. Upon BCR stimulation, the BCR ‐positive cell lines showed active BCR – PI 3K signalling and decreased MYC phosphorylation at T58, leading to an increased overall level of MYC . Conversely, inhibition of BCR – PI 3K signalling increased MYC phosphorylation and thus resulted in a decreased overall level of MYC . No effects were observed in the BCR ‐negative cell lines. Conclusions Overexpression of MYC in DLBCL can be driven by the BCR – PI 3K signalling pathway via dephosphorylation at T58, and BCR inhibitors may exert their functions by down‐regulation of MYC .