MYD88 in the driver's seat of B-cell lymphomagenesis: from molecular mechanisms to clinical implications.

MYD88 in the driver's seat of B-cell lymphomagenesis: from molecular mechanisms to clinical implications. Haematologica. 2019 Nov 07;: Authors: de Groen RAL, Schrader AMR, Kersten MJ, Pals ST, Vermaat JSP Abstract More than 50 subtypes of B-cell non-Hodgkin lymphoma are recognized in the most recent World Health Organization classification of 2016. The current treatment paradigm, however, is largely based on 'one-size-fits-all' immune-chemotherapy. Unfortunately, this therapeutic strategy is inadequate for a significant number of patients. As such, there is an indisputable need for novel, preferably targeted, therapies based on a biologically driven classification and risk stratification. Sequencing studies identified mutations in the MYD88 gene as an important oncogenic driver in B-cell lymphomas. MYD88 mutations constitutively activate the NF-κB and its associated signalling pathways, thereby promoting B-cell proliferation and survival. High frequencies of the hotspot MYD88 L265P mutation are observed in extranodal diffuse large B-cell lymphoma and Waldenström's macroglobulinemia, thereby demonstrating its potential as disease marker. In addition, the presence of mutant MYD88 predicts survival outcome in B-cell non-Hodgkin lymphoma subtypes and it provides a therapeutic target. Early clinical trials targeting MYD88, show encouraging results in relapsed/refractory B-cell non-Hodgkin lymphoma. These patients can benefit from analys...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research