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- W1970549013 startingPage "149" @default.
- W1970549013 abstract "Summary Chronic lymphocytic leukaemia ( CLL ) is an indolent B‐cell malignancy with heterogeneous outcomes. Chromosomal abnormalities in CLL are predictive of the natural disease course; del(11q) and del(17p) are recognized as high risk genetic lesions. Del(17p) is associated with an impaired function of TP 53, a key tumour suppressor, and is particularly problematic. Such patients respond poorly to chemo‐immunotherapy and have significantly shorter survival compared to patients with standard and low‐risk cytogenetics. While TP 53 pathway defects are rare at initial diagnosis, their frequency increases in relapsed CLL . Until very recently, this group of patients represented an unmet clinical need with few therapeutic options. However, the advent of targeted therapies has expanded the drug armamentarium and introduced new hope for these highly refractory patients. Agents that target B‐cell receptor signalling, BH 3‐mimetics and others induce apoptosis of the neoplastic B‐cells in a TP 53‐independent manner. Their use in the clinic is associated with remarkable activity in patients with del(17p). In this review we discuss the frequency and clinical significance of del(17p) and genetic mutations leading to disrupted TP 53, the putative role of other TP 53 homologues, and the results of key clinical trials involving both conventional chemotherapy and novel agents." @default.
- W1970549013 created "2016-06-24" @default.
- W1970549013 creator A5016570475 @default.
- W1970549013 creator A5020351745 @default.
- W1970549013 creator A5067633124 @default.
- W1970549013 date "2014-07-21" @default.
- W1970549013 modified "2023-10-03" @default.
- W1970549013 title "A new hope: novel therapeutic approaches to treatment of chronic lymphocytic leukaemia with defects in<i>TP53</i>" @default.
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