ArticleOncotarget2018
NKL homeobox gene NKX2-2 is aberrantly expressed in Hodgkin lymphoma.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Research on the potential mechanisms and therapeutic drug for the co-occurrence of major depressive disorder in castration-resistant prostate cancer.Scientific reports · 2025Article
- EWS/FLI1 Characterization, Activation, Repression, Target Genes and Therapeutic Opportunities in Ewing Sarcoma.International journal of molecular sciences · 2023Review
- Downregulation of STAT3 in Epstein-Barr Virus-Positive Hodgkin Lymphoma.Biomedicines · 2022Article
- Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia.Cancers · 2022Article
- Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci.Nature genetics · 2021Article
- NKL-Code in Normal and Aberrant Hematopoiesis.Cancers · 2021Review
- DAZAP2 acts as specifier of the p53 response to DNA damage.Nucleic acids research · 2021Article
- Establishment of the TALE-code reveals aberrantly activated homeobox gene PBX1 in Hodgkin lymphoma.PloS one · 2021Article
- Establishment of the TBX-code reveals aberrantly activated T-box gene TBX3 in Hodgkin lymphoma.PloS one · 2021Article
- The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL).Oncotarget · 2020Article
- NK homeobox 2.2 functions as tumor suppressor in colorectal cancer due to DNA methylation.Journal of Cancer · 2020Article
- Deregulated NKL Homeobox Genes in B-Cell Lymphoma.Cancers · 2019Review
- Deregulated expression of NKL homeobox genes in T-cell lymphomas.Oncotarget · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NKL homeobox genes encode basic transcriptional regulators of cell and tissue differentiation. Recently, we described a hematopoietic NKL-code comprising nine specific NKL homeobox genes expressed in normal hematopoietic stem cells, lymphoid progenitors and during lymphopoiesis, highlighting their physiological role in the development of T-, B- and NK-cells. Here, we identified aberrant expression of the non-hematopoietic neural NKL homeobox gene NKX2-2 in about 12% of both, classical Hodgkin lymphoma (HL) and nodular lymphocyte predominant (NLP) HL patients. The NKX2-2 expressing NLPHL-derived cell line DEV served as a model by analysing chromosomal configurations and expression profiling data to reveal activating mechanisms and downstream targets of this developmental regulator. While excluding chromosomal rearrangements at the locus of NKX2-2 we identified t(3;14)(p21;q32) resulting in overexpression of the IL17 receptor gene IL17RB via juxtaposition with the IGH-locus. SiRNA-mediated knockdown experiments demonstrated that IL17RB activated NKX2-2 transcription. Overexpression of IL17RB-cofactor DAZAP2 via chromosomal gain of 12q13 and deletion of its proteasomal inhibitor SMURF2 at 17q24 supported expression of NKX2-2. IL17RB activated transcription factors FLI1 and FOXG1 which in turn mediated NKX2-2 expression. In addition, overexpressed chromatin-modulator AUTS2 contributed to NKX2-2 activation as well. Downstream analyses indicated that NKX2-2 inhibits transcription of lymphoid NKL homeobox gene MSX1 and activates expression of basic helix-loop-helix factor NEUROD1 which may disturb B-cell differentiation processes via reported interaction with TCF3/E2A. Taken together, our data reveal ectopic activation of a neural gene network in HL placing NKX2-2 at its hub, highlighting a novel oncogenic impact of NKL homeobox genes in B-cell malignancies.
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