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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 06, 2008 |
| Title |
Normal human bone marrow CD34+ cells, promyelocytes, and neutrophils and PR9 cell line PML-RARA induction time course |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
To better understand the pathogenesis of acute promyelocytic leukemia (APL, FAB M3 AML), we identified genes that are expressed differently in APL cells compared to other acute myeloid leukemia subtypes, and to normal promyelocytes. Comparative gene expression analysis of 14 M3, 62 other AML (M0, M1, M2 and M4) and 5 enriched normal promyelocyte samples revealed a signature of 1,121 genes that are specifically dysregulated in M3 samples relative to other AML, and that do not simply represent normal promyelocyte expression (“M3-specific signature”). We used a novel, high throughput digital platform (Nanostring's nCounter system) to evaluate a subset of the most significantly dysregulated genes in 30 AML samples; 33 of 37 evaluable gene expression patterns were validated. In an additional analysis, we selected only genes that are dysregulated in M3 both compared to other AML subtypes, and to purified normal CD34+ cells, promyelocytes, and/or neutrophils, thereby isolating a 478 gene "composite M3 dysregulome". Surprisingly, the expression of only a few of these genes was significantly altered in PR-9 cells after PML-RARA induction, suggesting that most of these genes are not direct targets of PML-RARA. Comparison of the M3-specific signature to our previously described murine APL dysregulome revealed 33 commonly dysregulated genes, including JUN, EGR1, and TNF. Collectively, these results suggest that PML-RARA initiates a transcriptional cascade which generates a unique downstream expression signature in both primary human and mouse APL cells.
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| Overall design |
14 human APL/M3 AML samples were compared to 62 AML samples of other AML FAB subtypes (bone marrow aspirates collected at diagnosis, included in GSE10358), to fractionated cells from normal human bone marrow aspirates (5 CD34+ cells, 5 promyelocytes, 5 neutrophils/PMNs), and to PR9 cells before and after Zinc-induction of PML-RARA.
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| Contributor(s) |
Payton JE, Grieselhuber N, Ley TJ |
| Citation(s) |
19451695 |
| Submission date |
Sep 03, 2008 |
| Last update date |
Mar 25, 2020 |
| Contact name |
Jacqueline Payton |
| Organization name |
Washington University School of Medicine
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| Street address |
4320 Forest Park Avenue, Suite 211
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| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63108 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (106)
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| Relations |
| BioProject |
PRJNA113071 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12662_RAW.tar |
457.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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