Related Experiment Video
Updated: Aug 8, 2025
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
FLT3-TKD in the prognosis of patients with acute myeloid leukemia: A meta-analysis
Shuping Li1,2, Na Li1,2, Yun Chen1
1Edmond H. Fischer Translational Medical Research Laboratory, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
Background:
Fms-like tyrosine kinase 3 (FLT3) gene mutations occur in approximately 30% of all patients with acute myeloid leukemia (AML). Internal tandem duplication (ITD) in the juxtamembrane domain and point mutations within the tyrosine kinase domain (TKD) are two distinct types of FLT3 mutations. FLT3-ITD has been determined as an independent poor prognostic factor, but the prognostic impact of potentially metabolically related FLT3-TKD remains controversial. Hence, we performed a meta-analysis to investigate the prognostic significance of FLT3-TKD in patients with AML.
Methods:
A systematic retrieval of studies on FLT3-TKD in patients with AML was performed in PubMed, Embase, and Chinese National Knowledge Infrastructure databases on 30 September 2020. Hazard ratio (HR) and its 95% confidence intervals (95% CIs) were used to determine the effect size. Meta-regression model and subgroup analysis were used for heterogeneity analysis. Begg's and Egger's tests were performed to detect potential publication bias. The sensitivity analysis was performed to evaluate the stability of findings in meta-analysis.
Results:
Twenty prospective cohort studies (n = 10,970) on the prognostic effect of FLT3-TKD in AML were included: 9,744 subjects with FLT3-WT and 1,226 subjects with FLT3-TKD. We found that FLT3-TKD revealed no significant effect on disease-free survival (DFS) (HR = 1.12, 95% CI: 0.90-1.41) and overall survival (OS) (HR = 0.98, 95% CI: 0.76-1.27) in general. However, meta-regressions demonstrated that patient source contributed to the high heterogeneity observed in the prognosis of FLT3-TKD in AML. To be specific, FLT3-TKD represented a beneficial prognosis of DFS (HR = 0.56, 95% CI: 0.37-0.85) and OS (HR = 0.63, 95% CI: 0.42-0.95) for Asians, whereas it represented an adverse prognosis of DFS for Caucasians with AML (HR = 1.34, 95% CI: 1.07-1.67).
Conclusion:
FLT3-TKD revealed no significant effects on DFS and OS of patients with AML, which is consistent with the controversial status nowadays. Patient source (Asians or Caucasians) can be partially explained the different effects of FLT3-TKD in the prognosis of patients with AML.
Insights
Fms-like tyrosine kinase 3 (FLT3) tyrosine kinase domain (TKD) mutations do not significantly impact acute myeloid leukemia (AML) patient survival overall. However, FLT3-TKD prognosis differs by patient ethnicity, showing a beneficial effect in Asians and an adverse effect in Caucasians.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Fms-like tyrosine kinase 3 (FLT3) mutations are common in acute myeloid leukemia (AML).
- FLT3 internal tandem duplication (ITD) is a known poor prognostic factor.
- The prognostic significance of FLT3 tyrosine kinase domain (TKD) mutations in AML remains controversial.
Approach:
- A meta-analysis was conducted using data from 20 prospective cohort studies (n=10,970).
- Studies were systematically retrieved from PubMed, Embase, and CNKI databases.
- Hazard ratios (HR) and 95% confidence intervals (CIs) were used to assess prognostic effects, with meta-regression for heterogeneity analysis.
Key Points:
- FLT3-TKD mutations showed no significant impact on disease-free survival (DFS) or overall survival (OS) in AML patients globally.
- Meta-regression revealed patient ethnicity as a source of heterogeneity.
- FLT3-TKD was associated with a beneficial prognosis for DFS and OS in Asian patients, but an adverse prognosis for DFS in Caucasian patients.
Conclusions:
- FLT3-TKD mutations do not have a universally significant effect on AML patient prognosis.
- Patient ethnicity (Asian vs. Caucasian) partially explains the differing prognostic impacts of FLT3-TKD mutations in AML.
