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Published on: September 20, 2016
[Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute
Shan-Hao Tang1, Ying Lu1, Pi-Sheng Zhang1
1Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.
Objective:
To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML).
Methods:
Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation).
Results:
The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011).
Conclusion:
TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Insights
Translocator protein (TSPO) gene expression is significantly elevated in acute myeloid leukemia (AML) with FLT3-ITD/DNMT3A R882 mutations. Higher TSPO levels at diagnosis indicate a poorer response to chemotherapy, suggesting TSPO as a potential biomarker for treatment efficacy in this AML subtype.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Context:
- Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy.
- Specific genetic mutations, such as FLT3-ITD and DNMT3A R882, significantly impact AML prognosis and treatment response.
- Translocator protein (TSPO) is a mitochondrial protein implicated in various cellular processes, including cell proliferation and apoptosis.
Purpose:
- To investigate the clinical significance of translocator protein (TSPO) gene expression in patients with FLT3-ITD/DNMT3A R882 double-mutated AML.
- To evaluate TSPO as a potential biomarker for treatment efficacy in this specific AML subpopulation.
Summary:
- TSPO gene expression was analyzed in 76 AML patients, including those with FLT3-ITD, DNMT3A R882, and double FLT3-ITD/DNMT3A R882 mutations, compared to an immune thrombocytopenia control group.
- Patients with FLT3-ITD/DNMT3A R882 double mutations exhibited significantly higher TSPO gene expression at initial diagnosis compared to single mutation groups and controls.
- A significant decrease in TSPO gene expression was observed in FLT3-ITD/DNMT3A R882 mutated AML patients who achieved complete response post-chemotherapy, indicating its correlation with treatment outcome.
Impact:
- TSPO gene expression levels may serve as a predictive biomarker for treatment response in FLT3-ITD/DNMT3A R882 double-mutated AML.
- This finding could contribute to personalized treatment strategies for AML patients with these specific mutations.
- Further research into the functional role of TSPO in AML pathogenesis may reveal novel therapeutic targets.
