Overexpression of FLT3-ITD driven by spi-1 results in expanded myelopoiesis with leukemic phenotype in zebrafish
- Authors
- Lu, J.W., Hou, H.A., Hsieh, M.S., Tien, H.F., Lin, L.I.
- ID
- ZDB-PUB-160610-15
- Date
- 2016
- Source
- Leukemia 30(10): 2098-2101 (Journal)
- Registered Authors
- Lin, Liang-In, Lu, Jeng-Wei
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Myelopoiesis/genetics*
- Phenotype
- Proto-Oncogene Proteins/physiology*
- Trans-Activators/physiology*
- Zebrafish/embryology
- fms-Like Tyrosine Kinase 3/genetics
- fms-Like Tyrosine Kinase 3/metabolism*
- PubMed
- 27271227 Full text @ Leukemia
Acute myeloid leukemia (AML) is a clonal hematologic malignancy that shows great variability with regard to pathogenesis and treatment outcomes. The class III receptor tyrosine kinase of FMS-like tyrosine kinase 3 (FLT3) has an important role in normal hematopoiesis and internal tandem duplications of FLT3 (FLT3-ITD), which disrupts the autoinhibitory juxtamembrane domain, is one of the most common mutations in AML. The FLT3-ITD mutation is typically associated with poor prognosis and significantly increased relapse rates. Indeed, FLT3-ITD can induce growth factor-independent proliferation in leukemia cell lines and fetal myeloproliferative neoplasm (MPN) in murine models. Therefore, FLT3-ITD is considered a key driver of AML pathogenesis and may be an ideal therapeutic target for AML patients. Nucleophosmin (NPM1) is a multifunctional nucleus-cytoplasm shuttling protein known to be involved in the regulation of cell growth and proliferation.