Related Experiment Video
Updated: Sep 28, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
TYRO3 Knockdown Suppresses the Growth of Myeloid Leukaemia Cells
Tatsuya Saito1, Mai Itoh1, Shuji Tohda2
1Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Background/Aim:
TYRO3 is a member of the TAM family (TYRO3, AXL, and MERTK) of receptor tyrosine kinases. While the roles of activated AXL and MERTK in the growth of leukaemia cells have been reported, the effect of TYRO3 has not been determined. Therefore, we examined the effects of TYRO3 knockdown on the growth of leukaemia cell lines.
Materials And Methods:
Three human leukaemia cell lines (AA derived from pure erythroid leukaemia, OCI/AML2, and K562), which express TYRO3 protein were used in this study. To induce TYRO3 knockdown, small interfering RNA (siRNA) against TYRO3 was transfected using an electroporation system. Cell growth was assessed by a colorimetric assay. The expression levels and activation of various signalling proteins were examined by immunoblotting. Changes in comprehensive gene expression after TYRO3 knockdown were examined by microarray analysis.
Results:
TYRO3 knockdown suppressed cell growth in the leukaemia cell lines tested. Additionally, the knockdown suppressed phosphorylation of signal transducer and activator of transcription-3 in AA cells, and extracellular signal-regulated kinase (ERK) 1/2 in AA and OCI/AML2 cells; both are downstream molecules of TYRO3 signalling. TYRO3 knockdown also suppressed the expression of survivin in all the cell lines. TYRO3 knockdown potently suppressed TYRO3 mRNA expression but not that of AXL and MERTK. Furthermore, TYRO3 knockdown suppressed cyclin D1 mRNA expression, which is a downstream molecule of ERK.
Conclusion:
TYRO3 plays a role in leukaemia cell growth and is a potential therapeutic target for leukaemia.
Insights
TYRO3 receptor tyrosine kinase knockdown inhibited leukaemia cell growth by suppressing key signaling pathways. This suggests TYRO3 is a potential therapeutic target for treating leukaemia.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- TYRO3 is part of the TAM family of receptor tyrosine kinases.
- While AXL and MERTK roles in leukemia are known, TYRO3's effect is unclear.
Purpose of the Study:
- To investigate the impact of TYRO3 knockdown on leukaemia cell growth.
- To elucidate the downstream signaling pathways affected by TYRO3 in leukaemia.
Main Methods:
- Utilized three human leukaemia cell lines expressing TYRO3.
- Performed TYRO3 knockdown using small interfering RNA (siRNA) and electroporation.
- Assessed cell growth, protein activation via immunoblotting, and gene expression via microarray.
Main Results:
- TYRO3 knockdown significantly suppressed leukaemia cell growth.
- Downstream signaling molecules, including STAT3 and ERK1/2, showed reduced phosphorylation.
- Expression of survivin and cyclin D1 mRNA was decreased following TYRO3 knockdown.
Conclusions:
- TYRO3 plays a crucial role in the proliferation of leukaemia cells.
- TYRO3 represents a potential therapeutic target for leukaemia treatment.
More Related Videos
10:21Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
10:59Conditional Knockdown of Gene Expression in Cancer Cell Lines to Study the Recruitment of Monocytes/Macrophages to the Tumor Microenvironment
Published on: November 23, 2017
