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Published on: March 26, 2018
Clinical implications of PRAME gene expression in childhood acute myeloid leukemia
Daniel Steinbach1, Johann Hermann, Susanne Viehmann
1University Children's Hospital, Jena, Germany. danielsteinbach@hotmail.com
Insights
Preferentially expressed antigen of melanoma (PRAME) gene expression in childhood acute myeloid leukemia (AML) indicates a favorable prognosis. PRAME levels can monitor minimal residual disease, aiding treatment decisions.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Preferentially expressed antigen of melanoma (PRAME) is a gene implicated in various cancers.
- Its role in pediatric acute myeloid leukemia (AML) and prognostic significance requires further elucidation.
Purpose of the Study:
- To investigate PRAME gene expression in pediatric AML.
- To assess the correlation between PRAME expression and clinical outcomes, including survival and relapse.
- To evaluate PRAME expression in stem cells and its implications for immunotherapy.
Main Methods:
- Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was used to measure PRAME gene expression.
- Samples included newly diagnosed pediatric AML patients, healthy donor stem cells, bone marrow, peripheral blood, and AML cell lines.
- Eight patients were analyzed at relapse, with one patient monitored longitudinally.
Main Results:
- PRAME gene is expressed in CD34(+) stem cells, contrary to previous reports.
- Overexpression of PRAME was observed in 62% of pediatric AML patients.
- Higher PRAME expression correlated with improved overall and disease-free survival (P<0.05).
- PRAME expression was negatively correlated with white blood cell count and higher in patients with t(8;21).
- Expression levels at diagnosis corresponded with relapse levels (P<0.001), with increased levels preceding relapse in one monitored patient.
Conclusions:
- PRAME gene expression serves as a favorable prognostic indicator in childhood AML.
- PRAME expression levels can be a valuable tool for monitoring minimal residual disease in pediatric AML.
- The expression of PRAME in stem cells may pose challenges for PRAME-targeted immunotherapy.
Abstract:
The expression of the PRAME gene (preferentially expressed antigen of melanoma) was measured by quantitative reverse transcriptase polymerase chain reaction in 50 children with newly diagnosed acute myeloid leukemia (AML), three samples of CD34(+) stem cells, six bone marrow samples, and 10 peripheral blood samples of healthy donors, as well as three AML cell-lines (KG-1, U937, and HL-60). Eight patients were also analyzed in relapse. Contrary to previous reports, we could show that the PRAME gene is expressed by CD34(+) stem cells. This might constitute a problem in using PRAME for tumor immunotherapy. Overexpression of PRAME was found in 62% (n=31) of our patients. The rates of overall and disease-free survival in this group were higher than in patients with no or low expression (P<0.05). PRAME expression was negatively correlated to the white blood cell count at diagnosis (P<0.05) and significantly higher in patients with t(8;21). The levels of expression at diagnosis corresponded with those at relapse (P<0.001) and increased levels could be found prior to the relapse in one patient who was regularly monitored. Our results suggest that the expression of PRAME is an indicator of favorable prognosis and could be a useful tool for monitoring minimal residual disease in childhood AML.
