PUBLICATION
Irf8 regulates the progression of myeloproliferative neoplasm (MPN)-like syndrome via Mertk signaling in zebrafish
- Authors
- Zhao, F., Shi, Y., Huang, Y., Zhan, Y., Zhou, L., Li, Y., Wan, Y., Li, H., Huang, H., Ruan, H., Luo, L., Li, L.
- ID
- ZDB-PUB-170621-8
- Date
- 2017
- Source
- Leukemia 32(1): 149-158 (Journal)
- Registered Authors
- Huang, Honghui, Li, Li, Luo, Lingfei, Ruan, Hua
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified/genetics
- Cell Proliferation/genetics
- Disease Progression
- Gene Expression Regulation/genetics
- Interferon Regulatory Factors
- Myeloid Cells/pathology
- Myelopoiesis/genetics
- Myeloproliferative Disorders/genetics*
- Myeloproliferative Disorders/pathology*
- Signal Transduction/genetics*
- Zebrafish/genetics*
- c-Mer Tyrosine Kinase/genetics*
- PubMed
- 28626217 Full text @ Leukemia
Citation
Zhao, F., Shi, Y., Huang, Y., Zhan, Y., Zhou, L., Li, Y., Wan, Y., Li, H., Huang, H., Ruan, H., Luo, L., Li, L. (2017) Irf8 regulates the progression of myeloproliferative neoplasm (MPN)-like syndrome via Mertk signaling in zebrafish. Leukemia. 32(1):149-158.
Abstract
Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8 mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation. Multiple molecules presented notable alteration and Mertk signaling was aberrantly activated in the hematopoietic cells in irf8 mutants. Transgenic mertk overexpression in Tg(coro1a:mertk) zebrafish recapitulated the myeloid neoplasia-like syndrome in irf8 mutants. Moreover, functional interference with Mertk, via morpholino knockdown or genetic disruption, attenuated the myeloid expansion phenotype caused by Irf8 deficiency. Therefore, Mertk signaling is a critical downstream player in the Irf8-mediated regulation of the progression of myeloid neoplasia. Our study extends the understanding of the mechanisms underlying leukemogenesis.Leukemia accepted article preview online, 19 June 2017. doi:10.1038/leu.2017.189.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping