FLT3-TKD in the prognosis of patients with acute myeloid leukemia: A meta-analysis

Shuping Li; Na Li; Yun Chen; Zhihua Zheng; Yao Guo

doi:10.3389/fonc.2023.1086846

FLT3-TKD in the prognosis of patients with acute myeloid leukemia: A meta-analysis

Front Oncol. 2023 Feb 17:13:1086846. doi: 10.3389/fonc.2023.1086846. eCollection 2023.

Authors

Shuping Li^{1

2}, Na Li^{1

2}, Yun Chen¹, Zhihua Zheng², Yao Guo¹

Affiliations

¹ Edmond H. Fischer Translational Medical Research Laboratory, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
² Department of Nephrology, Center of Nephrology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China.

Abstract

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.

Keywords: AML; FLT3-TKD; meta-analysis; metabolism; prognosis.

Publication types

Systematic Review

Grants and funding

We thank National Natural Science Foundation of China (No. 82202579 and No. 81900673) and the Shenzhen Science and Technology Innovation Committee of Guangdong Province of China (Grant No. JCYJ20180307150634856, JCYJ20210324123200003) to support the study design, data analysis and publication of the manuscript.