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| Status |
Public on Aug 22, 2020 |
| Title |
The role of mesenchymal stromal cells (MSC) in the development of acute myeloid leukemia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic stem cells with a poor prognosis. It has been reported in many tumors that mesenchymal stem/ stromal cells (MSCs) support the growth of the malignant cells. In this study we analyzed the interaction between MSCs and AML cells in patients and in murine models of human AML. We found that MSCs from AML patients or leukemic mice supported the growth of AML cells in vitro better than MSCs originating from healthy mice or control persons. Interestingly, MSCs from AML patients who achieved complete remission didn’t support the growth of leukemia cells in vitro anymore. Due to the difficulty to obtain sufficient human MSCs, we developed a novel method to immortalize human MSCs. Immortalized MSC cells derived from AML patients also supported the growth of human AML cells better than MSC cells derived from a healthy donor. Among others, AMSCs increased entering of leukemic cells into cell cycle and at the same time protected the leukemia cells against exogenous toxic events such as chemotherapy or irradiation. In vivo, we observed an increase in the number of MSCs in the bone marrow of leukemic mice compared to healthy mice. Microarray data of AMSCs show upregulation of epithelial mesenchymal trasition genes. The polarization of MSCs towards an AML-supporting state depends on upregulated expression of the transcription factor Growth factor independence 1 (Gfi1). Loss of Gfi1 abrogated the tumor-supporting state of AML-associated MSCs. In summary, we report that MSCs support the growth of AML cells in a Gfi1-dependent manner.
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| Overall design |
3 mice which are KP8201, KP8203 and KP8966, were transplanted with BM transduced with MLL-AF9 while 3 mice which are KP1820, KP8816 and TU1777, were transplanted with normal BM cells. When the mice became sick, they were killed and the MSCs from the crushed bones were sorted for RNA study.
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| Contributor(s) |
Al-Matary YS, Khandanpour C, Vassan L, Klein-Hitpass L |
| Citation missing |
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| Submission date |
Aug 22, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Ludger Klein-Hitpass |
| E-mail(s) |
ludger.klein-hitpass@uni-essen.de
|
| Phone |
+49 201 723 85552
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| Organization name |
Institut fuer Zellbiologie
|
| Department |
Universitaetsklinikum
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| Lab |
BioChip Lab
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| Street address |
Virchowstr. 173
|
| City |
Essen |
| ZIP/Postal code |
D-45122 |
| Country |
Germany |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA399500 |
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