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| Status |
Public on Jun 18, 2019 |
| Title |
Deregulated expression of NKL homeobox genes in T-cell lymphomas |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Third-party reanalysis
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| Summary |
Homeobox genes encode transcription factors regulating basic processes in cell differentiation during embryogenesis and in the adult. Recently, we have reported the NKL-code which describes physiological expression patterns of nine NKL homeobox genes in early hematopoiesis and in lymphopoiesis including main stages of T-, B- and NK-cell development. Aberrant activity of NKL homeobox genes is involved in the generation of hematological malignancies including T-cell leukemia. Here, we searched for deregulated NKL homeobox genes in main entities of T-cell lymphomas comprising peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), adult T-cell leukemia/lymphoma (ATLL), hepatospleenic T-cell lymphoma (HSTL), and NK/T-cell lymphoma (NKTL). Our data revealed in all types altogether 19 aberrantly overexpressed genes, demonstrating that deregulated NKL homeobox genes play a significant role in T-cell lymphomas as well. For detailed analyses we focused on NKL homeobox gene MSX1 which is normally expressed in NK-cells and aberrantly activated in T-cell leukemia. This gene was overexpressed in subsets of HSTL patients and HSTL-derived sister cell lines DERL-2 and DERL-7 which served as models to identify mechanisms of deregulation. We performed genomic and expression profiling and whole genome sequencing and revealed mutated and deregulated gene candidates including the fusion gene CD53-PDGFRB exclusively expressed in DERL-2. Subsequent knockdown experiments allowed the construction of an aberrant network involved in MSX1 deregulation containing chromatin factors AUTS2 and H3B/H3.1, PDGF- and BMP-signalling pathways, and homeobox genes NKX2-2 and PITX1. The gene encoding AUTS2 is located at 7q11 and may represent a basic target of the HSTL hallmark aberration i(7q). Our data indicate both oncogenic and tumor suppressor functions of MSX1 in HSTL, reflecting its activity in early lineage differentiation of T- and NK-cells and the presence of NK-cell like characteristics in malignant HSTL cells. In this context, NKL homeobox gene MSX1 may represent a selective target in HSTL tumor evolution. Together, the data highlight an oncogenic role of deregulated NKL homeobox genes in T-cell lymphoma and identified MSX1 as a novel player in HSTL, involved in aberrant NK- and T-cell differentiation.
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| Overall design |
Deregulated expression of NKL homeobox genes in T-cell lymphomas
Data from 9 published samples were used in this study (IMC-1 and KHYG1 from GEO:GSE19067; NK-92 from GEO:GSE53478; SNK6 from GEO:GSE19067 and 5 T-ALL cell lines i.e. ALL-SIL, CCRF-CEM, PEER, JURKAT, LOUCY from GSE87334)
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| Contributor(s) |
Nagel S, Pommerenke C |
| Citation(s) |
31143370 |
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| Submission date |
Mar 14, 2019 |
| Last update date |
Jun 19, 2019 |
| Contact name |
Claudia Pommerenke |
| E-mail(s) |
[email protected]
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| Organization name |
Leibniz Institute DSMZ
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| Street address |
Inhoffenstraße 7B
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| City |
Braunschweig |
| ZIP/Postal code |
38124 |
| Country |
Germany |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (15)
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| Relations |
| Reanalysis of |
GSM471998 |
| Reanalysis of |
GSM472000 |
| Reanalysis of |
GSM1294333 |
| Reanalysis of |
GSM472006 |
| BioProject |
PRJNA527062 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128302_RAW.tar |
69.0 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE128302_complete_RMA_data.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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