The proliferation arrest of primary tumor cells out-of-niche is associated with widespread downregulation of mitotic and transcriptional genes

• Published in: Hematology (Luxembourg) Vol. 19; no. 5; pp. 286 - 292
• Main Authors: Cohen, Yossi, Gutwein, Odit, Garach-Jehoshua, Osnat, Bar-Haim, Adina, Kornberg, Abraham
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.07.2014
• Subjects: Bone Marrow - pathology; Cell Cycle Checkpoints - genetics; Cell Proliferation; Cluster Analysis; Computational Biology; Gene expression profile; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; IL8; Leukemia; Mitosis - genetics; Molecular Sequence Annotation; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Myeloma; Neoplasms - genetics; Niche; SPP1; SPP1; Niche; IL8; Myeloma; Leukemia; Gene expression profile
• ISSN: 1607-8454; 1607-8454
• DOI: 10.1179/1607845413Y.0000000125

In recording the changes acquired in gene expression profile during culture of fresh bone marrow samples from patients with multiple myeloma or acute myeloid leukemia, the most remarkable finding in both instances was widespread downregulation of mitotic and transcriptional genes (e.g. MKI67, CCNB1, ASPM, SGOL1, DLGAP5, CENPF, BUB1, KIF23, KIF18a, KIF11, KIF14, KIF4, NUF2, KIF1, AE2FB, TOP2A, NCAPG, TTK, CDC20, and AURKB), which could account for the ensuing proliferation arrest. Many of these genes were also underexpressed in leukemic cells from the blood or myeloma cells from an extramedullary site compared with their expression in the aspirates. Taken together, our results exhibited mitotic and transcriptional gene subsets where their expression appears to be coordinated and niche dependent. In addition, the genes induced during culture specified a variety of angiogenic factors (e.g. interleukin-8 and CXCL-5) and extracellular matrix proteins (e.g. osteopontin and fibronectin) probably released by the tumor cells while generating their favored microenvironment.