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| Status |
Public on Jan 04, 2013 |
| Title |
MCL1 is deregulated in subgroups of diffuse large B-cell lymphoma |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
|
| Summary |
MCL1 is an anti-apoptotic member of the BCL2 family that is deregulated in various solid and hematological malignancies. However, its role in the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL) is unclear. We analyzed gene expression profiling data from 350 DLBCL patient samples and detected that activated B-cell-like (ABC) DLBCLs express MCL1 at significantly higher levels compared to germinal center B-cell-like (GCB) DLBCL patient samples (p=2.7 x 10(-10)) [PMID 23257783]. Immunohistochemistry confirmed high MCL1 protein expression predominantly in ABC DLBCL in an independent patient cohort (n=249; p=0.001).
To elucidate molecular mechanisms leading to aberrant MCL1 expression, we analyzed array comparative genomic hybridization (aCGH) data of 203 DLBCL samples [GSE11318] and identified recurrent chromosomal gains/amplifications of the MCL1 locus that occurred in 26% of ABC DLBCLs. In addition, aberrant STAT3 signaling contributed to high MCL1 expression in this subtype. Knockdown of MCL1 as well as treatment with the BH3-mimetic obatoclax induced apoptotic cell death in MCL1 positive DLBCL cell lines. In summary, MCL1 is deregulated in a significant fraction of ABC DLBCLs and contributes to therapy resistance. These data suggest that specific inhibition of MCL1 might be utilized therapeutically in a subset of DLBCLs.
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| Overall design |
This GEO dataset is comprised of aCGH measurements for DLBCL cell lines, which are used in the above-mentioned paper. Cell lines were measured against the DNA of a healthy male donor who in turn was measured against a pool of healthy DNAs to correct for individual CNVs of the donor.
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| Contributor(s) |
Lenz G |
| Citation(s) |
23257783 |
| |
| Submission date |
Jan 03, 2013 |
| Last update date |
Oct 26, 2013 |
| Contact name |
Michael Grau |
| Organization name |
University of Münster
|
| Department |
Faculty of Medicine
|
| Lab |
Translational Oncology
|
| Street address |
Albert-Schweitzer-Campus 1
|
| City |
Münster |
| State/province |
Nordrhein-Westfalen |
| ZIP/Postal code |
48149 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL15436 |
NimbleGen Human CGH 3x720K Whole-Genome Tiling v3.0 Array [090527_HG18_WG_CGH_v3.1_HX3] |
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| Samples (13)
|
| GSM1059798 |
DNA pool versus male control DNA, 2 replicates |
| GSM1059799 |
DLBCL cell line OCI-Ly03 versus male control DNA |
| GSM1059800 |
DLBCL cell line OCI-Ly10 versus male control DNA |
| GSM1059801 |
DLBCL cell line TMD-8 versus male control DNA |
| GSM1059802 |
DLBCL cell line U2932 versus male control DNA |
| GSM1059803 |
DLBCL cell line OCI-Ly01 versus male control DNA |
| GSM1059804 |
DLBCL cell line HBL-1 versus male control DNA |
| GSM1059805 |
DLBCL cell line BJAB versus male control DNA |
| GSM1059806 |
DLBCL cell line HT versus male control DNA |
| GSM1059807 |
DLBCL cell line K422 versus male control DNA |
| GSM1059808 |
DLBCL cell line SUDHL-10 versus male control DNA |
| GSM1059809 |
DLBCL cell line OCI-Ly07 versus male control DNA |
| GSM1059810 |
DLBCL cell line OCI-Ly02 versus male control DNA |
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| Relations |
| BioProject |
PRJNA185203 |
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