TY - JOUR
T1 - The proliferation arrest of primary tumor cells out-of-niche is associated with widespread downregulation of mitotic and transcriptional genes
AU - Cohen, Yossi
AU - Gutwein, Odit
AU - Garach-Jehoshua, Osnat
AU - Bar-Haim, Adina
AU - Kornberg, Abraham
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
KW - Gene expression profile
KW - IL8
KW - Leukemia
KW - Myeloma
KW - Niche
KW - SPP1
UR - http://www.scopus.com/inward/record.url?scp=84902837005&partnerID=8YFLogxK
U2 - 10.1179/1607845413Y.0000000125
DO - 10.1179/1607845413Y.0000000125
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AN - SCOPUS:84902837005
SN - 1024-5332
VL - 19
SP - 286
EP - 292
JO - Hematology
JF - Hematology
IS - 5
ER -