Identification of genes modulated in multiple myeloma using genetically identical twin samples

Nikhil C. Munshi, Teru Hideshima, Daniel Carrasco, Masood Shammas, Daniel Auclair, Faith Davies, Nicholas Mitsiades, Constantine Mitsiades, Ryung S. Kim, Cheng Li, S. Vincent Rajkumar, Rafael Fonseca, Lief Bergsagel, Dharminder Chauhan, Kenneth C. Anderson

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Genetic heterogeneity between individuals confounds the comparison of gene profiling of multiple myeloma (MM) cells versus normal plasma cells (PCs). To overcome this barrier, we compared the gene expression profile of CD138 + MM cells from a patient bone marrow (BM) sample with CD138 + PCs from a genetically identical twin BM sample using microarray profiling. Two hundred and ninety-six genes were up-regulated and 103 genes were down-regulated at least 2-fold in MM cells versus normal twin PCs. Highly expressed genes in MM cells included cell survival pathway genes such as mcl-1, dad-1, caspase 8, and FADD-like apoptosis regulator (FLIP); oncogenes/transcriptional factors such as Jun-D, Xbp-1, calmodulin, Calnexin, and FGFR-3; stress response and ubiquitin/proteasome pathway-related genes and various ribosomal genes reflecting increased metabolic and translational activity. Genes that were down-regulated in MM cells versus healthy twin PCs included RAD51, killer cell immunoglobulin-like receptor protein, and apoptotic protease activating factor. Microarray results were further confirmed by Western blot analyses, immunohistochemistry, fluorescent in situ hybridization (FISH), and functional assays of telomerase activity and bone marrow angiogenesis. This molecular profiling provides potential insights into mechanisms of malignant transformation in MM. For example, FGFR3, xbp-1, and both mcl-1 and dad-1 may mediate transformation, differentiation, and survival, respectively, and may have clinical implications. By identifying genes uniquely altered in MM cells compared with normal PCs in an identical genotypic background, the current study provides the framework to identify novel therapeutic targets.

Original languageEnglish (US)
Pages (from-to)1799-1806
Number of pages8
JournalBlood
Volume103
Issue number5
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

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Monozygotic Twins
Multiple Myeloma
Genes
Plasma Cells
Plasmas
Bone
Bone Marrow
Microarrays
Calnexin
Far-Western Blotting
KIR Receptors
Genetic Heterogeneity
Caspase 8
Telomerase
Proteasome Endopeptidase Complex
Calmodulin
Ubiquitin
Fluorescence In Situ Hybridization
Oncogenes
Transcriptome

ASJC Scopus subject areas

  • Hematology

Cite this

Munshi, N. C., Hideshima, T., Carrasco, D., Shammas, M., Auclair, D., Davies, F., ... Anderson, K. C. (2004). Identification of genes modulated in multiple myeloma using genetically identical twin samples. Blood, 103(5), 1799-1806. https://doi.org/10.1182/blood-2003-02-0402

Identification of genes modulated in multiple myeloma using genetically identical twin samples. / Munshi, Nikhil C.; Hideshima, Teru; Carrasco, Daniel; Shammas, Masood; Auclair, Daniel; Davies, Faith; Mitsiades, Nicholas; Mitsiades, Constantine; Kim, Ryung S.; Li, Cheng; Rajkumar, S. Vincent; Fonseca, Rafael; Bergsagel, Lief; Chauhan, Dharminder; Anderson, Kenneth C.

In: Blood, Vol. 103, No. 5, 01.03.2004, p. 1799-1806.

Research output: Contribution to journalArticle

Munshi, NC, Hideshima, T, Carrasco, D, Shammas, M, Auclair, D, Davies, F, Mitsiades, N, Mitsiades, C, Kim, RS, Li, C, Rajkumar, SV, Fonseca, R, Bergsagel, L, Chauhan, D & Anderson, KC 2004, 'Identification of genes modulated in multiple myeloma using genetically identical twin samples', Blood, vol. 103, no. 5, pp. 1799-1806. https://doi.org/10.1182/blood-2003-02-0402
Munshi NC, Hideshima T, Carrasco D, Shammas M, Auclair D, Davies F et al. Identification of genes modulated in multiple myeloma using genetically identical twin samples. Blood. 2004 Mar 1;103(5):1799-1806. https://doi.org/10.1182/blood-2003-02-0402
Munshi, Nikhil C. ; Hideshima, Teru ; Carrasco, Daniel ; Shammas, Masood ; Auclair, Daniel ; Davies, Faith ; Mitsiades, Nicholas ; Mitsiades, Constantine ; Kim, Ryung S. ; Li, Cheng ; Rajkumar, S. Vincent ; Fonseca, Rafael ; Bergsagel, Lief ; Chauhan, Dharminder ; Anderson, Kenneth C. / Identification of genes modulated in multiple myeloma using genetically identical twin samples. In: Blood. 2004 ; Vol. 103, No. 5. pp. 1799-1806.
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