XBP1s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatments
T Bagratuni, P Wu… - Blood, The Journal …, 2010 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2010•ashpublications.org
Immunoglobulin production by myeloma plasma cells depends on the unfolded protein
response for protein production and folding. Recent studies have highlighted the importance
of IRE1α and X box binding protein 1 (XBP1), key members of this pathway, in normal B-
plasma cell development. We have determined the gene expression levels of IRE1 α, XBP1,
XBP1 UNSPLICED (XBP1u), and XBP1 SPLICED (XBP1s) in a series of patients with
myeloma and correlated findings with clinical outcome. We show that IRE1 α and XBP1 are …
response for protein production and folding. Recent studies have highlighted the importance
of IRE1α and X box binding protein 1 (XBP1), key members of this pathway, in normal B-
plasma cell development. We have determined the gene expression levels of IRE1 α, XBP1,
XBP1 UNSPLICED (XBP1u), and XBP1 SPLICED (XBP1s) in a series of patients with
myeloma and correlated findings with clinical outcome. We show that IRE1 α and XBP1 are …
Abstract
Immunoglobulin production by myeloma plasma cells depends on the unfolded protein response for protein production and folding. Recent studies have highlighted the importance of IRE1α and X box binding protein 1 (XBP1), key members of this pathway, in normal B-plasma cell development. We have determined the gene expression levels of IRE1α, XBP1, XBP1UNSPLICED (XBP1u), and XBP1SPLICED (XBP1s) in a series of patients with myeloma and correlated findings with clinical outcome. We show that IRE1α and XBP1 are highly expressed and that patients with low XBP1s/u ratios have a significantly better overall survival. XBP1s is an independent prognostic marker and can be used with β2 microglobulin and t(4;14) to identify a group of patients with a poor outcome. Furthermore, we show the beneficial therapeutic effects of thalidomide in patients with low XBP1s/u ratios. This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response. This trial was registered at www.controlled-trials.com/ISRCTN68454111/68454111 as #ISRCTN684541111.
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