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APRIL promotes cell cycle progression in primary multiple myeloma cells: influence of D-type cyclin group and translocation status

Quinn, J; Glassford, J; Percy, L; Munson, P; Marafioti, T; Rodriguez-Justo, M; Yong, K; (2010) APRIL promotes cell cycle progression in primary multiple myeloma cells: influence of D-type cyclin group and translocation status. Blood

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Abstract

A Proliferation Inducing Ligand (APRIL) promotes survival and drug resistance in MM cell lines. We studied the effect of APRIL on cell cycle behaviour in primary MM cells and correlated our findings with D-type cyclin expression by immunohistochemistry (IHC) and/or western blotting. In MM cases expressing cyclin D2, APRIL significantly increased the percentage of CD138+ cells in S+G2/M phase (from 8.4 +/- 1.9% to 14.3 +/- 2.6%, n=15, p<0.01) while a lesser effect was seen in cases expressing cyclin D1 (n=18). Cell cycle response to APRIL was most marked for cyclin D2 expressing cases with IgH translocations (p<0.01) and was accompanied by increased expression of cyclin D2, CDK4, CDK6 and phospho-pRb proteins. Cell cycle proteins in cyclin D1+ cells were not modulated by APRIL. Surface expression of BCMA and TACI was not significantly different between cyclin D1+ and D2+ MM cells. We observed activation of NFkappaB and PI3-kinase pathways in response to APRIL in both cyclin D1+ and D2+ MM cells. In conclusion, APRIL stimulates G1/S progression in cyclin D2+ MM cells bearing IgH translocations, but has minimal effect on cyclin D1+ cells, suggesting MM cells from different cyclin D/translocation classes rely on different mechanisms for cell-cycle re-entry.

Type: Article
Title: APRIL promotes cell cycle progression in primary multiple myeloma cells: influence of D-type cyclin group and translocation status
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1321397
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