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Targeting Oncoprotein Translation with Rocaglates in MYC-Driven Lymphoma
Background: c-MYC (MYC) is commonly dysregulated in aggressive B cell lymphomas. MYC associated lymphoma, especially Double Hit lymphoma (DHL) and Double-Expression Lymphoma (DEL) which are characterized by MYC and BCL2 dual overexpression usually present with the inferior outcome as rapid disease progression and poor response to standard chemotherapy regimen. Nevertheless, MYC is considered as an "undruggable" target and targeting strategies such as suppressing MYC transcription by bromodomain (BRD)-4 inhibitors have been widely investigated in both preclinical models and clinical trials. However, increasing evidence has ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, X., Bi, C., Lu, T., Yue, T., Zhang, W., Zhang, X., Cheng, W., Tian, T., Lunning, M. A., Vose, J. M., Pelletier, J., Porco, J. A., Tao, J., Fu, K. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Specific Pathway Inhibitors Source Type: research

CD55 and CD59 Can Limit the Anti-Tumor Efficacy of Daratumumab in Natural Killer/T-Cell Lymphoma
In this report we show that subsequent testing in an NKTL mouse xenograft model confirms the potency of Daratumumab in vivo as evidenced by the inhibition in tumour progression and prolongation of mouse survival. When treatment was continued over a month, some tumors began to rapidly enlarge ('Resistant') while the rest remained similar or smaller ('Sensitive') than the tumour volume at the initiation of Daratumumab treatment. An mRNA analysis comparing 'Resistant' and 'Sensitive' tumors showed that while both tumours bore similar levels of CD38 expression, resistant tumours displayed an upregulation of complement inhibito...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mustafa, N., Nee, A. H. F., Chooi, J. Y., Toh, S. H. M., Hee, Y. T., Selvarajan, V., Zhou, L., Yang, J., Chng, W. J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster I Source Type: research

Overexpressed Melk Promotes the Stability of EZH2 through Phosphorylation in Natural Killer/T Cell Lymphoma (NKTL)
In this study, we examined EZH2 protein turnover mechanisms in the NKTL context.The serine/threonine kinase Melk is one of the overexpressed genes in NKTL patient samples and cell lines, and the interaction between Melk and EZH2 was established by co-immunoprecipitation. Inhibition of Melk using inhibitor or siRNA both resulted in a decrease of EZH2 protein levels in NKTL cells, whereas there was no change in the mRNA level of EZH2, suggesting that Melk regulated EZH2 at the protein level. Next, we observed a change of EZH2 ubiquitination upon manipulation of Melk expression.Next, in order to confirm that Melk truly affect...
Source: Blood - November 21, 2018 Category: Hematology Authors: Li, B., Kappei, D., Yan, J., Eichhorn, P., Ng, S. B., Chng, W. J. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster II Source Type: research