Targeting CD19 in diffuse large B-cell lymphoma: An expert opinion paper.

The ubiquitous, early-stage expression, efficient internalization, limited off-target effects, and high disease specificity of CD19 make it an attractive therapeutic target. Currently available anti-CD19 therapies have demonstrated particular promise in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Selection of the most appropriate treatment strategy should be based on individual patient characteristics and the goal of therapy. However, evidence and knowledge about the sequencing of anti-CD19 therapies are limited. Here, we review the current evidence for CD19 as a target in diffuse large B-cell lymphoma and consider approaches to the use of anti-CD19 therapy

Targeting CD19 in diffuse large B-cell lymphoma : An expert opinion paper

Medical writing assistance was provided by Sarah Stowell of Alligent Europe (Envision Pharma Group), funded by Incyte Biosciences International Sàrl.The ubiquitous, early-stage expression, efficient internalization, limited off-target effects, and high disease specificity of CD19 make it an attractive therapeutic target. Currently available anti-CD19 therapies have demonstrated particular promise in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Selection of the most appropriate treatment strategy should be based on individual patient characteristics and the goal of therapy. However, evidence and knowledge about the sequencing of anti-CD19 therapies are limited. Here, we review the current evidence for CD19 as a target in diffuse large B-cell lymphoma and consider approaches to the use of anti-CD19 therapy

Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms

This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities