| RRC ID |
43758
|
| Author |
Sivina M, Hartmann E, Vasyutina E, Boucas JM, Breuer A, Keating MJ, Wierda WG, Rosenwald A, Herling M, Burger JA.
|
| Title |
Stromal cells modulate TCL1 expression, interacting AP-1 components and TCL1-targeting micro-RNAs in chronic lymphocytic leukemia.
|
| Journal |
Leukemia
|
| Abstract |
The tissue microenvironment in chronic lymphocytic leukemia (CLL) has an increasingly recognized role in disease progression, but the molecular mechanisms of cross talk between CLL cells and their microenvironment remain incompletely defined. Bone marrow stromal cells (BMSC) protect CLL cells from apoptosis in a contact-dependent fashion, and have been used for the identification of key pathways such as the CXCR4-CXCL12 axis. To further dissect the molecular impact of BMSC on survival and the molecular activation signature of CLL cells, we co-cultured CLL cells with different BMSC. Gene expression profiling of CLL cells revealed that the lymphoid proto-oncogene TCL1 was among the top genes upregulated in CLL cells by BMSC. TCL1 mRNA and protein upregulation by BMSC was paralleled by decreases of TCL1-interacting FOS/JUN, and confirmed by qRT-PCR, immunoblotting, immunoprecipitations, and flow cytometry. Stroma mediated increases in TCL1 were also associated with decreased levels of TCL1-regulatory micro-RNAs (miR-29b, miR-181b, miR-34b). These findings demonstrate that the microenvironment has a proactive role in the regulation of the known signaling enhancer and pro-survival molecule TCL1 in CLL. This provides a further rationale for therapeutically targeting the cross talk between CLL and BMSC.
|
| Volume |
26(8)
|
| Pages |
1812-20
|
| Published |
2012-8-1
|
| DOI |
10.1038/leu.2012.63
|
| PII |
leu201263
|
| PMID |
22460735
|
| MeSH |
Bone Marrow Cells / metabolism
Cell Communication
Cell Survival / drug effects
Cluster Analysis
Coculture Techniques
Gene Expression Profiling
Gene Expression Regulation, Leukemic*
Humans
Interleukin-4 / pharmacology
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
MicroRNAs / genetics*
MicroRNAs / metabolism
Myeloid Cell Leukemia Sequence 1 Protein
Proto-Oncogene Mas
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Proto-Oncogene Proteins c-fos / genetics
Proto-Oncogene Proteins c-jun / genetics
Stromal Cells / metabolism*
Transcription Factor AP-1 / metabolism*
Transcription, Genetic
|
| IF |
8.665
|
| Times Cited |
30
|
|
WOS Category
|
ONCOLOGY
HEMATOLOGY
|
| Resource |
| Human and Animal Cells |
StromaNKtert(RCB2350)
KUSA-H1(RCB1990) |
