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Review
. 2019 Sep 5;11(9):1311.
doi: 10.3390/cancers11091311.

The Impact of Flt3 Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis

Gledson L Picharski  1   2 , Diancarlos P Andrade  1   2 , Ana Luiza M R Fabro  1   2   3 , Luana Lenzi  1   4 , Fernanda S Tonin  4 , Raul C Ribeiro  5 , Bonald C Figueiredo  6   7   8   9
Affiliations
Review

The Impact of Flt3 Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis

Gledson L Picharski et al. Cancers (Basel). .

Abstract

The association of FLT3 mutations with white blood cell (WBC) counts at diagnosis and early death was studied in patients with acute promyelocytic leukemia (APL). Publications indexed in databases of biomedical literature were analyzed. Potential publication bias was evaluated by analyzing the standard error in funnel plots using the estimated relative risk (RR). Mixed-effect models were used to obtain the consolidated RR. All analyses were conducted using the R statistical software package. We used 24 publications in the final meta-analysis. Of 1005 males and 1376 females included in these 24 publications, 645 had FLT3-ITD (internal tandem duplication) mutations. Information on FLT3-D835 mutations was available in 10 publications for 175 patients. Concurrent occurrence of the two mutations was rare. WBC count at diagnosis was ≥10 × 109/L in 351 patients. For patients with the FLT3-ITD mutation, RR was 0.59 for overall survival (OS) and 1.62 for death during induction. For those with FLT3-D835 mutations, the RR was 0.50 for OS and 1.77 for death during induction. RR for WBC count ≥10 × 109/L was 3.29 and 1.48 for patients with FLT3-ITD and FLT3-D835, respectively. APL patients with FLT3-ITD or FLT3-D835 are more likely to present with elevated WBC counts and poorer prognosis than those without these mutations.

Keywords: APL; FLT3-D835; FLT3-ITD; WBC; acute promyelocytic leukemia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart to identify studies on acute promyelocytic leukemia with the acquired mutations FLT3-ITD (internal tandem duplication) and FLT3-D835.
Figure 2
Figure 2
Risk of bias evaluation of each included study. (A) Risk of bias graph; (B) Risk of bias summary.
Figure 3
Figure 3
Meta-analysis of the relative risk (RR) by white blood cell count for FLT3-ITD (A) and FLT3-D835 (B) mutations. Mixed effect models were used for analysis. G: white blood cell count equal or greater than 10 × 109/L and L lower than 10 × 109/L. The numbers in each column represent the number of cases (patients).
Figure 4
Figure 4
Meta-analysis of the relative risk for patients with the FLT3-ITD mutation. Induction death (A), complete remission (B), and overall survival (C). Mixed effects models were used for analysis. D: Deceased patients; S: Surviving patients; R: Complete Remission; and PR: Partial Remission. Cases positive or negative for FLT3-ITD or FLT3-D835 were divided into deceased patients and surviving patients. The numbers in each column represent the number of cases (patients).
Figure 4
Figure 4
Meta-analysis of the relative risk for patients with the FLT3-ITD mutation. Induction death (A), complete remission (B), and overall survival (C). Mixed effects models were used for analysis. D: Deceased patients; S: Surviving patients; R: Complete Remission; and PR: Partial Remission. Cases positive or negative for FLT3-ITD or FLT3-D835 were divided into deceased patients and surviving patients. The numbers in each column represent the number of cases (patients).
Figure 5
Figure 5
Meta-analysis of the relative risk for patients with the FLT3-D835 mutation. Induction death (A), complete remission (B), and overall survival (C). Mixed effects models were used for analysis. D: Deceased patients; S: Surviving patients; R: Complete Remission; and PR: Partial Remission. Cases positive or negative for FLT3-ITD or FLT3-D835 were divided into deceased patients and surviving patients. The numbers in each column represent the number of cases (patients).
Figure 5
Figure 5
Meta-analysis of the relative risk for patients with the FLT3-D835 mutation. Induction death (A), complete remission (B), and overall survival (C). Mixed effects models were used for analysis. D: Deceased patients; S: Surviving patients; R: Complete Remission; and PR: Partial Remission. Cases positive or negative for FLT3-ITD or FLT3-D835 were divided into deceased patients and surviving patients. The numbers in each column represent the number of cases (patients).
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