Nakagawa, R., Vukovic, M., Cosimo, E. and Michie, A. M. (2012) Modulation of PKC-α promotes lineage reprogramming of committed B lymphocytes. European Journal of Immunology, 42(4), pp. 1005-1015. (doi: 10.1002/eji.201141442)
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Publisher's URL: http://dx.doi.org/10.1002/eji.201141442
Abstract
During hematopoietic lineage development, HSCs sequentially commit towards myeloid or lymphoid lineages in a tightly regulated manner, which under normal circumstances is irreversible. However, studies have established that targeted deletion of the B lineage-specific transcription factor, paired box gene 5 (Pax5), enables B cells to differentiate towards other hematopoietic lineages, in addition to generating progenitor B cell lymphomas. Our previous studies showed that subversion of PKCα in developing B cells transforms B lineage cells. Here we demonstrate that PKCα modulation in committed CD19+ B lymphocytes also promotes lineage conversion towards myeloid, NK and T cell lineages upon Notch ligation. This occurs via a reduction in Pax5 expression resulting from a downregulation of E47, a product of the E2A gene. T cell lineage commitment is indicated by the expression of T cell associated genes, Ptcra, Cd3e and gene rearrangement at the Tcrb gene locus. Importantly, the lineage converted T cells carry Igh gene rearrangements reminiscent of their B cell origin. Our findings suggest that modulation of PKCα induces hematopoietic lineage plasticity in committed B lineage cells by perturbing expression of critical B lineage transcription factors, and deregulation of PKCα activity/expression represents a potential mechanism for lineage trans-differentiation during malig
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Michie, Professor Alison and Cosimo, Dr Emilio and Vukovic, Ms Milica and Nakagawa, Dr Rinako |
| Authors: | Nakagawa, R., Vukovic, M., Cosimo, E., and Michie, A. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | European Journal of Immunology |
| Journal Abbr.: | Eur. J. Immunol. |
| Publisher: | Wiley-VCH Verlag |
| ISSN: | 0014-2980 |
| ISSN (Online): | 1521-4141 |
| Related URLs: |
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