Browse by author
Lookup NU author(s): Dr Jeyanthy Eswaran, Dr Paul Sinclair, Professor Olaf Heidenreich, Professor Julie Irving, Dr Lisa Russell, Dr Andrew Hall, Professor Christine Harrison FRCPath FMedSci, Dr Britta Vormoor
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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.
Author(s): Eswaran J, Sinclair P, Heidenreich O, Irving J, Russell LJ, Hall A, Calado DP, Harrison CJ, Vormoor J
Publication type: Review
Publication status: Published
Journal: Leukemia
Year: 2015
Volume: 29
Issue: 8
Pages: 1623-1631
Print publication date: 01/08/2015
Online publication date: 22/05/2015
Acceptance date: 23/04/2015
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: NATURE PUBLISHING GROUP
URL: http://dx.doi.org/10.1038/leu.2015.113
DOI: 10.1038/leu.2015.113
