Differential Expression of Genes in Multiple Myeloma (MM) and Identification of Candidates to Targeted Therapy.

Abstract

Considering the heterogeneity of genetic aspects related with MM pathogenesis, recent studies have been focused on prognostic factors that could define the best therapeutic approach for each case or to contribute for the development of new therapies. In this way, gene expression profiling analysis can be very helpful to define such prognostic factors. Serial analysis of gene expression (SAGE) allows not only the identification of genes expressed in a given tissue, but also their expression levels. Until now, there was no data of gene expression in normal or neoplastic plasmacytes in public SAGE databases.Purpose: The aim of this study is to create two SAGE libraries using normal and neoplastic plasmacytes and to identify genes differentially expressed in MM.Methods: Normal plasmacytes were obtained from palatine tonsils of children who underwent tonsillectomy. MM library was obtained from bone marrow plasmacytes of two IgGk newly diagnosed MM patients. Purified normal and neoplastic plasmacytes were obtained after magnetic sorting of CD-138-positive cells (MACS - Magnetic Cell Sorting of Human Cells, Miltenyi Biotec). Both SAGE libraries were obtained using the kit I-SAGE (Invitrogen), according to manufacture's instructions.Results: We generated 4,000 clones from each library and, after automatic sequencing, we got 29,918 tags from normal and 10,340 tags from tumoral libraries (corresponding to 8,241 and 2,359 unique tags, respectively). After comparison of unique tags expression levels, we selected 15 overexpressed (at least 10 times) genes in the MM library (ZFHX1B, XBP1, PIM2, LGALS1, RANBP2, HSPC132, PRDM2, DDX5, ARMCX3, LSM5, JUND, MAPKAPK2, SP140, KLF2 and NTN1). Once these genes are related with transcription, signaling, cell proliferation and/or apoptosis, they can have important role in the tumorigenesis process and may be possible therapeutic targets for MM control