کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8429436 1546206 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
MYC deregulation in lymphoid tumors: molecular mechanisms, clinical consequences and therapeutic implications
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
MYC deregulation in lymphoid tumors: molecular mechanisms, clinical consequences and therapeutic implications
چکیده انگلیسی
MYC is one of the most frequently deregulated oncogenes in human malignancies. It encodes a leucine zipper transcription factor that modulates a broad spectrum of cellular genes responsible for enhancing cell proliferation, cellular metabolism, growth, angiogenesis, metastasis, genomic instability, stem cell self-renewal and reduced differentiation. MYC functions predominantly as an amplifier of expression of already active genes, potentiating the pre-existing transcriptional program, although it can also repress certain transcriptional targets. In mouse models, MYC induces lymphomas, but requires cooperation with other lesions, including inactivation of the p53 pathway, structural alterations of BCL2 family members, or increased PI3K activity. In human B-cell tumors, MYC rearrangements involving the 8q24 region and immunoglobulin heavy or light genes are a hallmark of Burkitt lymphoma (BL), but can also occur in other lymphoid malignancies, that include diffuse large B-cell lymphoma (DLBCL), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU), plasma cell myeloma (PCM), mantle cell lymphoma (MCL) and plasmablastic lymphoma. For non-BL lymphoid malignancies, MYC fusions represent secondary genetic events and exist in the context of complex karyotypes. Regardless of the mechanism deregulating MYC, lymphomas over-expressing MYC are addicted to this oncogene, highlighting the potential clinical utility of MYC targeting strategies. Several promising approaches for pharmaceutical intervention have been suggested which are now in preclinical or clinical development. Herein, we therefore review the molecular pathogenetic mechanisms associated with MYC deregulation in human B-cell lymphomas and their implications for therapies targeting MYC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer - Volume 1846, Issue 2, December 2014, Pages 457-467
نویسندگان
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