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| Status |
Public on Jan 19, 2017 |
| Title |
NKL homeobox gene activities in hematopoietic stem cells, T-cell development and T-cell leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
T-cell acute lymphoblastic leukemia (T-ALL) cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem cells (HSCs) and during lymphopoiesis, identifying activities of 9 particular genes. Four of these were expressed in HSCs (HHEX, HLX1, NKX2-3 and NKX3-1) and three in common lymphoid progenitors (HHEX, HLX1 and MSX1). Interestingly, our data indicated downregulation of NKL homeobox gene transcripts in late progenitors and mature T-cells, a phenomenon which might explain the oncogenic impact of this group of genes in T-ALL. Using MSX1-expressing T-ALL cell lines as models, we showed that HHEX activates while HLX1, NKX2-3 and NKX3-1 repress MSX1 transcription, demonstrating the mutual regulation and differential activities of these homeobox genes. Analysis of a public T-ALL expression profiling data set comprising 117 patient samples identified 20 aberrantly activated members of the NKL subclass, extending the number of known NKL homeobox oncogene candidates. While 7/20 genes were also active during hematopoiesis, the remaining 13 showed ectopic expression. Finally, comparative analyses of T-ALL patient and cell line profiling data of NKL-positive and NKL-negative samples indicated absence of common target genes but instead highlighted deregulation of apoptosis as common oncogenic effect. Taken together, we present a comprehensive survey of NKL homeobox genes in early hematopoiesis, T-cell development and T-ALL, showing that these genes generate an NKL-code for the diverse stages of lymphoid development which might be fundamental for regular differentiation.
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| Overall design |
NKL positive T-ALL cell lines were compared to NKL negative
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| Contributor(s) |
Nagel S, Pommerenke C |
| Citation(s) |
28151996 |
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| Submission date |
Sep 26, 2016 |
| Last update date |
Mar 25, 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 (11)
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| Relations |
| BioProject |
PRJNA344440 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE87334_RAW.tar |
50.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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