Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays

Abstract

Our previous studies have characterized Dexamethasone (Dex)-induced apoptotic signaling pathways in multiple myeloma (MM) cells; however, related transcriptional events are not fully de®ned. In the present study, gene expression pro®les of Dex-treated MM cells were determined using oligonucleotide arrays. Dex triggers early transient induction of many genes involved in cell defense/repair-machinery. This is followed by induction of genes known to mediate cell death and repression of growth/survival-related genes. The molecular and genetic alterations associated with Dex resistance in MM cells are also unknown. We compared the gene expression pro®les of Dex-sensitive and Dex-resistant MM cells and identi®ed a number of genes which may confer Dexresistance. Finally, gene pro®ling of freshly isolated MM patient cells validates our in vitro MM cell line data, con®rming an in vivo relevance of these studies. Collectively, these ®ndings provide insights into the basic mechanisms of Dex activity against MM, as well as mechanisms of Dex-resistance in MM cells. These studies may therefore allow improved therapeutic uses of Dex, based upon targeting genes that regulate MM cell growth and survival.

Glucocorticoid receptor transcriptional isoforms and resistance in multiple myeloma cells

“…It should be noted that RNAs used for real-time RT-PCR were obtained from independent experiments, further verifying the changes. Our data are consistent with a previous report showing low levels of GRa in MM.1R cells by Northern blot and oligonucleotide arrays (35,36).…”

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results

“…Myeloma regimens are commonly augmented with dexamethasone (dex), which often improves response rates to other agents (Sonneveld & Broijl, 2016). BTK expression was upregulated at both the protein and mRNA levels in MM1R dex‐resistant cells, suggesting a possible role of BTK in the mechanism of dex resistance (Chauhan et al , 2002). …”

Gene expression shift towards normal B cells, decreased proliferative capacity and distinct surface receptors characterize leukemic blasts persisting during induction therapy in childhood acute lymphoblastic leukemia

“…The majority of genes were assigned to the functional groups cell cycle regulation (47), metabolism (216), cell communication and stress response (104) and apoptosis (20). In addition, some genes (14) were manually annotated with known functions in B-cell differentiation and development. Table 1 shows a subset of the d8/d0 gene set consisting of the top 20 representatives of each functional group.…”

“…[6][7][8][9][10] It has also led to a large set of genes, which are potentially involved in GC response. [11][12][13][14][15] Accordingly, the hypotheses generated to explain the cytotoxic activity of GC are explicitly diverse, reaching from the direct activation of the apoptotic machinery to indirect deregulations of cellular functions, such as nucleotide and protein synthesis, energy metabolism, pH state and redox homeostasis. 11,12,16 Most studies have focused on gene expression in experimental cell systems.…”