4.7 Article Proceedings Paper

Genetic landscape and deregulated pathways in B-cell lymphoid malignancies

期刊

JOURNAL OF INTERNAL MEDICINE
卷 282, 期 5, 页码 371-394

出版社

WILEY
DOI: 10.1111/joim.12633

关键词

B-cell lymphomas; deregulated pathways; genetic aberrations; next-generation sequencing; prognosis

资金

  1. Swedish Cancer Society
  2. Swedish Research Council
  3. Karolinska Institutet Uppsala University
  4. Uppsala University Hospital
  5. Lion's Cancer Research Foundation
  6. Selander's Foundation, Uppsala
  7. Fondo de Investigaciones Sanitarias
  8. Instituto de Salud Carlos III [PI14/00571]
  9. Fundacio La Marato de TV3-Cancer [2013410]
  10. Generalitat de Catalunya Suport Grups de Recerca [2013-SGR-378]
  11. European Regional Development Fund 'Una manera de fer Europa'
  12. CERCA Programme/Generalitat de Catalunya
  13. Bloodwise, UK
  14. Kay Kendal Leukaemia Fund, UK
  15. Institut Carnot on Lymphoma (CALYM)
  16. fondation ARC pour la recherche sur le cancer
  17. Institut National du cancer (INCa)
  18. Canceropole PACA
  19. Swedish Childhood Cancer Fund
  20. Center for Innovative Medicine at Karolinska Institutet (CIMED)

向作者/读者索取更多资源

With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma. We will detail recurrent alterations affecting important signalling pathways, that is the B-cell receptor/NF-kappa B pathway, NOTCH signalling, JAK-STAT signalling, p53/DNA damage response, apoptosis and cell cycle regulation, as well as other perhaps unexpected cellular processes, such as immune regulation, cell migration, epigenetic regulation and RNA processing. Whilst many of these pathways/processes are commonly altered in different lymphoid tumors, albeit at varying frequencies, others are preferentially targeted in selected B-cell malignancies. Some of these genetic lesions are either involved in disease ontogeny or linked to the evolution of each disease and/or specific clinicobiological features, and some of them have been demonstrated to have prognostic and even predictive impact. Future work is especially needed to understand the therapy-resistant disease, particularly in patients treated with targeted therapy, and to identify novel targets and therapeutic strategies in order to realize true precision medicine in this clinically heterogeneous patient group.

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