TY - JOUR
T1 - Recent advances in the pathogenesis and treatment of chronic lymphocytic leukemia
AU - Efremov, Dimitar G.
AU - Laurenti, Luca
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Humans
KW - Leukemia, Lymphocytic, Chronic, B-Cell
KW - Receptors, Antigen, B-Cell
KW - Humans
KW - Leukemia, Lymphocytic, Chronic, B-Cell
KW - Receptors, Antigen, B-Cell
UR - http://hdl.handle.net/10807/135399
M3 - Article
SN - 0351-3254
VL - 35
SP - 105
EP - 120
JO - Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za bioloiki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences.
JF - Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za bioloiki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences.
ER -