El rol del receptor de células B y la señalización en el microambiente en la progresión de la leucemia linfoide crónica

• Dighiero, G. ^[1]
  1. [1] Institut Pasteur

     Institut Pasteur

     Francia

     
• Localización: Revista Hematología, ISSN 0329-0379, ISSN-e 2250-8309, Vol. 22, Nº. Extra 2, 2018 (Ejemplar dedicado a: 3er IBAM CLL 2018), págs. 15-21
• Idioma: español
• Títulos paralelos:
  • The role of B-cell receptor and microenvironment signalling in chronic lymphocytic leukemia progression
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• Resumen

  • Despite significant progress in treatment, CLL remains an incurable disease. Advances have been made to understand the molecular pathogenesis underlying CLL progression and treatment resistance. We here review the available evidences concerning the role of the B-cell receptor (BCR) and the tumour microenvironment interactions in CLL pathogenesis. Antigen likely plays a key role in the selection of the tumoral clone, the mutational status of Ig genes is a strong prognostic predictor and BCR signaling has been postulated to play a role for CLL trafficking and interaction with the stromal microenvironment. There is also important evidence favoring a role for the microenvironment in CLL pathogenesis. Most, if not all, proliferative events occur in lymph nodes and bone marrow, where leukemic cells receive through microenvironment interactions survival signals aiming to avoid apoptosis and acquire favourable tumoral growing conditions. In addition, the tumoral microenvironment appears to be the site where acquisition of additional genetic lesions in the clone occur, which should greatly influence clinical outcome. The advent of new tyrosine kinase inhibitors which seem to be able to modulate microenvironment interactions and circumvent the p53 deletion have generated significant promise by raising the possibility that they could provide significant progress in disease treatment. In this article we will discuss the following questions: 1) What is the role of the B-cell receptor (BCR) in CLL pathogenesis?, 2) What is the role of microenvironment in CLL progression?