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Molecular Subtyping in Diffuse Large B Cell Lymphoma: Closer to an Approach of Precision Therapy

  • Lymphoma (JW Sweetenham, Section Editor)
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Opinion Statement

It has become clear that there is immense biological heterogeneity in diffuse large B cell lymphoma (DLBCL). Developing technology has allowed better characterization of patient subsets at a molecular level, allowing for a link of phenotype and clinical outcomes to oncogenic mechanisms and biologic signatures. Cell of origin and double hit status are able to identify aggressive subsets, with molecular profiling allowing for a clearer understanding of biologic pathways that contribute to cellular resistance to conventional treatment in these subsets. Although the standard treatment for DLBCL remains R-CHOP or R-CHOP-like therapy at present, rational drug targets have been established with novel classes of drugs under investigation. In germinal center (GC) DLBCL, mechanisms of therapeutic interest include anti-apoptosis mediated by BCL-2, PI3K/AKT/mTOR, and EZH2, whereas drug interventions are directed at BCR, NF-κB, and/or JAK-STAT pathways in activated B cell (ABC) DLBCL. There is also evidence for cooperation of various oncogenic pathways in these subsets. As such, we are arguably on the verge of shifting to a more tailored approach using single and combinatorial strategies—this, however, relies on prioritizing the exploration of biomarkers for patient selection for validating novel treatment strategies.

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Correspondence to Reem Karmali MD, MS.

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Reem Karmali has received compensation from Celgene for serving on speakers’ bureaus and from Pharmacyclics and Seattle Genetics for service as a consultant.

Leo I. Gordon declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Lymphoma

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Karmali, R., Gordon, L.I. Molecular Subtyping in Diffuse Large B Cell Lymphoma: Closer to an Approach of Precision Therapy. Curr. Treat. Options in Oncol. 18, 11 (2017). https://doi.org/10.1007/s11864-017-0449-1

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  • DOI: https://doi.org/10.1007/s11864-017-0449-1

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