A molecular compendium of genes expressed in multiple myeloma

Abstract

We have created a molecular resource of genes expressed in primary malignant plasma cells using a combination of cDNA library construction, 5 end single-pass sequencing, bioinformatics, and microarray analysis. In total, we identified 9732 nonredundant expressed genes. This dataset is available as the Myeloma Gene Index (www.uhnres.utoronto.ca/akstewart_lab). Predictably, the sequenced profile of myeloma cDNAs mirrored the known function of immunoglobulin-producing, highrespiratory rate, low-cycling, terminally differentiated plasma cells. Nevertheless, approximately 10% of myeloma-expressed sequences matched only entries in the database of Expressed Sequence Tags (dbEST) or the high-throughput genomic sequence (htgs) database. Numerous novel genes of potential biologic significance were identified. We therefore spotted 4300 sequenced cDNAs on glass slides creating a myeloma-enriched microarray. Several of the most highly expressed genes identified by sequencing, such as a novel putative disulfide isomerase (MGC3178), tumor rejection antigen TRA1, heat shock 70-kDa protein 5, and annexin A2, were also differentially expressed between myeloma and B lymphoma cell lines using this myelomaenriched microarray. Furthermore, a defined subset of 34 up-regulated and 18 down-regulated genes on the array were able to differentiate myeloma from nonmyeloma cell lines. These not only include genes involved in B-cell biology such as syndecan, BCMA, PIM2, MUM1/IRF4, and XBP1, but also novel uncharacterized genes matching sequences only in the public databases. In summary, our expressed gene catalog and myelomaenriched microarray contains numerous genes of unknown function and may complement other commercially available arrays in defining the molecular portrait of this hematopoietic malignancy.

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

“…Several studies have demonstrated near universal BCMA expression in PCM cell lines and primary patient PCM cells, and signaling through BCMA provides a survival signal to myeloma cells and promotes resistance to antimyeloma therapies. [92][93][94][95][96] BCMA surface expression appears higher in PCM cells compared with normal plasma cells, and protein expression has not been reported in other normal cells or tissues, other than some mature B-cell subsets and plasmacytoid DC. 97,98 Carpenter et al 97 demonstrated that BCMA-redirected CAR T cells could proliferate, degranulate and produce cytokines when exposed to BCMA-expressing targets and could specifically kill PCM cell lines and primary patient PCM cells.…”

GAREM, a Novel Adaptor Protein for Growth Factor Receptor-bound Protein 2, Contributes to Cellular Transformation through the Activation of Extracellular Signal-regulated Kinase Signaling

“…In our study, only a single protein band of GAREM was detected in the lysate of certain types of cultured cells such as COS-7, HeLa, 293, and A431 cells (data not shown). The expression of the GAREM gene (FLJ21610) has been identified by microarray analysis of multiple myeloma cells (35). Further, this gene is hypomethylated in various human colorectal carcinoma cell lines (36).…”

mTOR, A New Therapeutic Target in Acute Myeloid Leukemia

“…157 In fact, pim-2 is dysregulated in lymphomas, leukemias including AML and several myelomas. [158][159][160][161] It has been postulated that Pim-2 blocks apoptosis. It has been postulated that Pim-2 blocks apoptosis through phosphorylation of the proapoptotic Bad protein.…”