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Publication : Genetics of diffuse large B-cell lymphoma.

First Author  Pasqualucci L Year  2018
Journal  Blood Volume  131
Issue  21 Pages  2307-2319
PubMed ID  29666115 Mgi Jnum  J:264227
Mgi Id  MGI:6192964 Doi  10.1182/blood-2017-11-764332
Citation  Pasqualucci L, et al. (2018) Genetics of diffuse large B-cell lymphoma. Blood 131(21):2307-2319
abstractText  Diffuse large B-cell lymphoma (DLBCL), the most frequent subtype of lymphoid malignancy, remains a significant clinical challenge, as approximately 30% of patients are not cured. Over the past decade, remarkable progress has been made in the understanding of the pathogenesis of this disease, spurred by the implementation of powerful genomic technologies that enabled the definition of its genetic and epigenetic landscape. These studies have uncovered a multitude of genomic alterations that contribute to the initiation and maintenance of the tumor clone by disrupting biological functions known to be critical for the normal biology of its cells of origin, germinal center B cells. The identified alterations involve epigenetic remodeling, block of differentiation, escape from immune surveillance, and the constitutive activation of several signal transduction pathways. This wealth of new information offers unique opportunities for the development of improved diagnostic and prognostic tools that could help guide the clinical management of DLBCL patients. Furthermore, a number of the mutated genes identified are potentially actionable targets that are currently being explored for the development of novel therapeutic strategies. This review summarizes current knowledge of the most common genetic alterations associated with DLBCL in relation to their functional impact on the malignant transformation process, and discusses their clinical implications for mechanism-based therapeutics.
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