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The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia
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The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia
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Journal Article
The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia
2015
Overview
The B-cell receptor (BCR) and its immature form, the precursor-BCR (pre-BCR), have a central role in the control of B-cell development, which is dependent on a sequence of cell-fate decisions at specific antigen-independent checkpoints. Pre-BCR expression provides the first checkpoint, which controls differentiation of pre-B to immature B-cells in normal haemopoiesis. Pre-BCR signalling regulates and co-ordinates diverse processes within the pre-B cell, including clonal selection, proliferation and subsequent maturation. In B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), B-cell development is arrested at this checkpoint. Moreover, malignant blasts avoid clonal extinction by hijacking pre-BCR signalling in favour of the development of BCP-ALL. Here, we discuss three mechanisms that occur in different subtypes of BCP-ALL: (i) blocking pre-BCR expression; (ii) activating pre-BCR-mediated pro-survival and pro-proliferative signalling, while inhibiting cell cycle arrest and maturation; and (iii) bypassing the pre-BCR checkpoint and activating pro-survival signalling through pre-BCR independent alternative mechanisms. A complete understanding of the BCP-ALL-specific signalling networks will highlight their application in BCP-ALL therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Acute lymphoblastic leukemia
/ Animals
/ Antigens
/ Antineoplastic Agents - therapeutic use
/ B cells
/ Humans
/ Leukemia
/ Medicine
/ Oncology
/ Pre-B Cell Receptors - antagonists & inhibitors
/ Pre-B Cell Receptors - metabolism
/ Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism
/ Precursor Cell Lymphoblastic Leukemia-Lymphoma - prevention & control
/ review
/ Survival
