Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma

Cyrus V. Hedvat, Raymond L. Comenzo, Julie Teruya-Feldstein, Adam B. Olshen, Scott A. Ely, Keren Osman, Yana Zhang, Nagesh Kalakonda, Stephen D Nimer

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Malignant plasma cells generally grow within the bone marrow microenvironment; however, they can also grow at extramedullary sites. To identify the tumour-specific alterations required for extramedullary growth, we analysed the expression profiles of a series of plasma cell neoplasms including primary multiple myeloma (MM), plasma cell leukaemia (PCL) and extramedullary plasmacytoma (EPC). Hierarchical clustering analysis segregated the EPCs from the remaining samples, and revealed an expression pattern associated with angiogenesis in the EPCs, involving higher expression of the genes TIE2, NOTCH3, CD31 and endoglin. Direct comparison of EPC samples with the MM samples identified 156 genes significantly upregulated and 85 genes significantly downregulated (P < 0.005, t-test) in the EPCs, including several genes involved in angiogenesis and adhesion that were upregulated (including angiopoietin 1. SPARC, Notch3 and fibronectin 1). Immunohistochemical staining demonstrated CD31 and endoglin protein expression in the EPC tumour cells, which are both angiogenesis related and could confer malignant plasma cells with the ability to grow outside the normal bone marrow environment. Defining how malignant plasma cell growth is regulated in the bone marrow versus at extramedullary sites will help to delineate the mechanisms underlying the dependence of tumour cell growth on angiogenesis and cell adhesion.

Original languageEnglish
Pages (from-to)728-744
Number of pages17
JournalBritish Journal of Haematology
Volume122
Issue number5
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

Plasmacytoma
Plasma Cells
Multiple Myeloma
Bone Marrow
Plasma Cell Neoplasms
Growth
Plasma Cell Leukemia
Angiopoietin-1
Genes
Neoplasms
Fibronectins
Cell Adhesion
Cluster Analysis
Down-Regulation
Staining and Labeling
Gene Expression
erucylphosphocholine
Endoglin

Keywords

  • Angiogenesis
  • Gene arrays
  • Multiple myeloma
  • Myeloma
  • Myeloma cell lines

ASJC Scopus subject areas

  • Hematology

Cite this

Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma. / Hedvat, Cyrus V.; Comenzo, Raymond L.; Teruya-Feldstein, Julie; Olshen, Adam B.; Ely, Scott A.; Osman, Keren; Zhang, Yana; Kalakonda, Nagesh; Nimer, Stephen D.

In: British Journal of Haematology, Vol. 122, No. 5, 01.09.2003, p. 728-744.

Research output: Contribution to journalArticle

Hedvat, Cyrus V. ; Comenzo, Raymond L. ; Teruya-Feldstein, Julie ; Olshen, Adam B. ; Ely, Scott A. ; Osman, Keren ; Zhang, Yana ; Kalakonda, Nagesh ; Nimer, Stephen D. / Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma. In: British Journal of Haematology. 2003 ; Vol. 122, No. 5. pp. 728-744.
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