Dataset Information

Stabilization of the c-Myc Protein by CAMKII? Promotes T Cell Lymphoma.

ABSTRACT: Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca2+/calmodulin-dependent protein kinase II ? (CAMKII?) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKII? was shown to be essential for tumor maintenance. Inhibition of CAMKII? with a specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high CAMKII? levels in patient TCL specimens correlate with increased c-Myc and pS62-c-Myc levels. Together, the CAMKII?:c-Myc axis critically influences the development and maintenance of TCL and represents a potential therapeutic target for TCL.

SUBMITTER: Gu Y

PROVIDER: S-EPMC5552197 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma.

Gu Ying Y Zhang Jiawei J Ma Xiaoxiao X Kim Byung-Wook BW Wang Hailong H Li Jinfan J Pan Yi Y Xu Yang Y Ding Lili L Yang Lu L Guo Chao C Wu Xiwei X Wu Jun J Wu Kirk K Gan Xiaoxian X Li Gang G Li Ling L Forman Stephen J SJ Chan Wing-Chung WC Xu Rongzhen R Huang Wendong W

Cancer cell 20170701 1

Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca<sup>2+</sup>/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabiliz ...[more]

PMID: 28697340

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Project description:Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (≥ 40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology.

Dataset Information

Stabilization of the c-Myc Protein by CAMKII? Promotes T Cell Lymphoma.

Publications

Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma.

Similar Datasets

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