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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 12, 2009 |
| Title |
Molecular variability of FLT3/ITD mutants and their impact on the differentiation program of 32D cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
FLT3 is the most frequently mutated gene in AML – up to 40% of AML harbor an activating mutation within FLT3 gene. Though AML is a relatively rare disease, such a high mutability rate, as observed with FLT3 gene, is striking. To elucidate the molecular background of this phenomenon, we have established nine unique FLT3/ITD - carrying 32D cell lines and a set of controls, and subjected them to whole genome expression analysis and 2DE LC/MS proteomics. Data obtained on this so far largest set of ITD mutants indicates that in comparison to the wild type FLT3 expressing 32D cells and transduction controls, FLT3/ITD positive cells exhibit less mature expression profiles resembling ST-HSC and MkEP/CMP/LMPP progenitors. We hypothesize that FLT3/ITD might contribute not only to the proliferative advantage of FLT3/ITD positive cells, but also to their reprogramming towards less differentiated stages, thus strengthening their malignant properties. This finding might explain the pronounced mutation rate of the aberrantly expressed FLT3 gene in AML, and, also, the inferior prognosis of FLT3/ITD positive AML patients. Moreover, the microarray data has revealed biological differences among individual ITD variants – a finding supporting the recent clinical data on the prognostic impact of the size of individual ITDs.
Keywords: genetic modification
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| Overall design |
Nine stable 32D cell lines harboring unique human FLT3/ITD mutants, two parental 32 cell lines, two 32D stable cell lines harboring cloning vector only, and two 32D cell lines stably expressing human wild type FLT3 were subjected to the microarray analysis.
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| Contributor(s) |
Pekova S, Ivanek R, Dvorak M, Rueggeberg S, Leicht S, Kozak T, Vrba J, Schwarz J, Cetkovsky P, Prucha M |
| Citation(s) |
19181379 |
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| Submission date |
Sep 12, 2008 |
| Last update date |
Mar 03, 2017 |
| Contact name |
Robert Ivanek |
| Phone |
+41 61 207 35 41
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| Organization name |
University of Basel
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| Department |
Department of Biomedicine
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| Lab |
Bioinformatics
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| Street address |
Hebelstrasse 20
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| City |
Basel |
| ZIP/Postal code |
4053 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL6193 |
[MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [probe set (exon) version] |
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| Samples (17)
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| GSM320268 |
32D, trasducted with mt FLT3 number A046 |
| GSM320269 |
32D, trasducted with mt FLT3 number A264 |
| GSM320270 |
32D, trasducted with mt FLT3 number A405 |
| GSM320271 |
32D, trasducted with mt FLT3 number A419 |
| GSM320272 |
32D, trasducted with mt FLT3 number A425 |
| GSM320273 |
32D, trasducted with mt FLT3 number A492 |
| GSM320274 |
32D, trasducted with mt FLT3 number A725 |
| GSM320275 |
32D, trasducted with mt FLT3 number B056 |
| GSM320276 |
32D, trasducted with empty pLXRN vector, biological rep1 |
| GSM320277 |
32D, trasducted with empty pLXRN vector, biological rep2 |
| GSM320278 |
32D, trasducted with wt FLT3, biological rep1 |
| GSM320279 |
32D, trasducted with wt FLT3, biological rep2 |
| GSM320280 |
32D, trasducted with wt FLT3 Ligand, biological rep1 |
| GSM320281 |
32D, trasducted with wt FLT3 Ligand, biological rep2 |
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| Relations |
| BioProject |
PRJNA111025 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12766_RAW.tar |
388.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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