<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Chronic lymphocytic leukaemia (CLL) is a common lymphoid malignancy characterized by the expansion and progressive accumulation of mature autoreactive B lymphocytes. The disease is clinically heterogeneous and incurable by standard chemotherapy. A major feature of the disease is the marked dependence of the leukaemic cells on various microenvironmental stimuli, which promote leukaemia cell growth, survival, and drug-resistance. Recently, considerable progress has been made in the understanding of the molecular mechanisms that drive CLL. The identification of recurrent genetic lesions using next generation sequencing technology has provided new data on the pathophysiology of the disease and has improved its prognostication. The recognition of the critical role of the B cell receptor (BCR) in driving the disease has resulted in the development of BCR pathway inhibitors that have the potential to completely transform CLL treatment in the near future. Other novel therapeutic agents, such as BCL2 antagonists and chimeric antigen receptor (CAR)-modified T-cells, are also showing great promise in clinical trials. In this review, we summarize some of these recent advances, with a particular focus on the BCR and corresponding pathway inhibitors.</p></abstract>

Chronic lymphocytic leukaemia (CLL) is a common lymphoid malignancy characterized by the expansion and progressive accumulation of mature autoreactive B lymphocytes. The disease is clinically heterogeneous and incurable by standard chemotherapy. A major feature of the disease is the marked dependence of the leukaemic cells on various microenvironmental stimuli, which promote leukaemia cell growth, survival, and drug-resistance. Recently, considerable progress has been made in the understanding of the molecular mechanisms that drive CLL. The identification of recurrent genetic lesions using next generation sequencing technology has provided new data on the pathophysiology of the disease and has improved its prognostication. The recognition of the critical role of the B cell receptor (BCR) in driving the disease has resulted in the development of BCR pathway inhibitors that have the potential to completely transform CLL treatment in the near future. Other novel therapeutic agents, such as BCL2 antagonists and chimeric antigen receptor (CAR)-modified T-cells, are also showing great promise in clinical trials. In this review, we summarize some of these recent advances, with a particular focus on the BCR and corresponding pathway inhibitors.

Recent Advances in the Pathogenesis and Treatment of Chronic Lymphocytic Leukemia

PRILOZI

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Chronic lymphocytic leukaemia (CLL) is a common lymphoid malignancy characterized by the expansion and progressive accumulation of mature autoreactive B...

Recent Advances in the Pathogenesis and Treatment of Chronic Lymphocytic Leukemia

Publié en ligne: 01 mars 2015

Pages: 105 - 120

DOI: https://doi.org/10.1515/prilozi-2015-0015

Mots clés
chronic lymphocytic leukaemia, B-cell receptor, fostamatinib, ibrutinib, idelalisib

© 2015 Dimitar G. Efremov and Luca Laurenti

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Recent Advances in the Pathogenesis and Treatment of Chronic Lymphocytic Leukemia

Publié en ligne: 01 mars 2015

Pages: 105 - 120

DOI: https://doi.org/10.1515/prilozi-2015-0015

Mots cléschronic lymphocytic leukaemia, B-cell receptor, fostamatinib, ibrutinib, idelalisib

© 2015 Dimitar G. Efremov and Luca Laurenti

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
chronic lymphocytic leukaemia, B-cell receptor, fostamatinib, ibrutinib, idelalisib