Refining the prognostic impact of the cell of origin in diffuse large B-cell lymphoma

<span class="paragraphSection">Efforts to understand the heterogeneous group of diffuse large B-cell lymphomas (DLBCL) have led to the identification of two major molecular subtypes based on the gene expression profile (GEP) related to different cells of origin (COO) either in germinal center (GCB) or activated B-cells (ABC) [<a href="#mdx133-B1" class="reflinks">1</a>, <a href="#mdx133-B2" class="reflinks">2</a>]. In addition to the GEP, these two molecular subtypes differ in the activation of different molecular pathways, profile of chromosomal alterations and somatic mutations. GCB tumors rely preferentially on the activation of the PI3K pathway and BCL6 overexpression whereas ABC tumors have a constitutive activation of the NFkB through different mechanisms including the activation of the BCR signaling pathway [<a href="#mdx133-B3" class="reflinks">3–7</a>]. These biological differences translate into different patient outcomes, with most of the studies showing worse prognosis for ABC than GCB-DLBCL even after the introduction of Rituximab [<a href="#mdx133-B1" class="reflinks">1</a>, <a href="#mdx133-B2" class="reflinks">2</a>]. The recognition of these two molecular subtypes is becoming more relevant with the progressive development of new therapeutic strategies that may preferentially benefit one of the two subtypes [<a href="#mdx133-B6" class="reflinks">6</a>]. Based on these perspectives, the updated 2016 WHO classification now requires that pathologists recognize these two DLBCL subtypes in the clinical practice, although the methodology to fulfil this need is not yet clearly established [<a href="#mdx133-B8" class="reflinks">8</a>]. </span>

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