Genomics

Dataset Information

0

Classical and/or alternative NF-kB pathway activation in multiple myeloma pathogenesis


ABSTRACT: Mutations involving the NFKB pathway are present in at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCL). These mutations, which are thought to be progression events, enable MM tumors to become less dependent on extrinsic bone marrow signals that activate NFKB. Studies on a panel of 50 MMCL provide some clarification of the mechanisms through which these mutations act and the significance of classical vs alternative activation of NFKB. First, only one mutation (NFKB2) selectively activates the alternative pathway, whereas several mutations (CYLD, NFKB1, TACI) selectively activate the classical pathway. However, most mutations affecting NIK level (NIK, TRAF2, TRAF3, cIAP1&2, CD40) activate the alternative but often both pathways. Second, we confirm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated proteosomal degradation of NIK in MM. Third, using transfection to selectively activate the classical or alternative NFKB pathways, we show virtually identical changes in gene expression in one MMCL, whereas the changes are similar albeit non-identical in a second MMCL. Together, our results suggest that MM tumors can achieve increased autonomy from the bone marrow microenvironment by mutations that activate either NFKB pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18047 | GEO | 2009/09/11

SECONDARY ACCESSION(S): PRJNA119303

REPOSITORIES: GEO

Similar Datasets

2013-12-01 | GSE52435 | GEO
| E-GEOD-52435 | biostudies-arrayexpress
2015-09-15 | GSE31272 | GEO
2007-10-29 | GSE8477 | GEO
2007-10-29 | GSE8476 | GEO
| E-GEOD-10422 | biostudies-arrayexpress
2008-02-28 | GSE10422 | GEO
2014-11-29 | GSE63702 | GEO
| EGAS00001000622 | EGA
| E-GEOD-68317 | biostudies-arrayexpress