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| Status |
Public on May 31, 2020 |
| Title |
NKL homeobox gene activity in normal and malignant myeloid cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Recently, we have reported a hematopoietic NKL-code which describes normal expression patterns of NKL homeobox genes in early hematopoiesis and lymphopoiesis including T-cell, B-cell and NK-cell development. This code allows the identification of deregulated NKL homeobox genes in lymphoid malignancies. Here, we report normal activities of NKL homeobox genes in myelopoiesis, thus, extending the NKL-code for the hematopoietic system. Analysis of public expression profiling data for developing and mature granulocytes, mast cells, monocytes, macrophages, megakaryocytes and erythrocytes revealed seven active myeloid NKL homeobox genes including DLX2, HHEX, HLX, HMX1, NANOG, NKX3-1 and VENTX. Furthermore, we analyzed public expression profiling data of 251 acute myeloid leukemia (AML) patients identifying 18 deregulated genes. These results indicated that NKL homeobox genes are frequently deregulated in this myeloid malignancy. For detailed analysis we focused on NKL homeobox gene NANOG which acts as stem cell factor and was accordingly expressed just in hematopoietic stem/progenitor cells. We detected aberrant NANOG expression in a small subset of AML patients and in AML cell line NOMO-1 which served as model to investigate upstream and downstream factors of this gene. Karyotyping and genomic profiling excluded rearrangements of the NANOG locus at 12p13. Analysis of NOMO-1 cells treated for NANOG knockdown, expression profiling analyses of HL-60 cells lentivirally transfected for NANOG overexpression, and of public AML patient data revealed regulators and target genes of NANOG. NKL homeobox genes HHEX and MSX1 and the NOTCH-pathway were located upstream of NANOG and HHEX, HLX, VENTX, MYB, CDK6, MAML2 and MIR17HG represented target genes of NANOG in the myeloid context. In conclusion, we described a myeloid NKL-code and several deregulated NKL homeobox genes in AML. We identified for NKL homeobox gene NANOG deregulating factors and downstream activities in AML. These data indicate a common oncogenic role of NKL homeobox genes in myeloid malignancies.
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| Overall design |
Expression profiling analyses of HL-60 cells lentivirally transfected for NANOG overexpression.
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| Contributor(s) |
Nagel S, Pommerenke C |
| Citation(s) |
31825998 |
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| Submission date |
May 13, 2019 |
| Last update date |
Sep 03, 2020 |
| 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 (4)
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| Relations |
| BioProject |
PRJNA542669 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE131113_RAW.tar |
19.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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