Journal
BIOENGINEERED
Volume 12, Issue 2, Pages 11987-12002Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2021.2001182
Keywords
4Ig B7-H3; 2Ig B7-H3; acute myeloid leukemia; prognosis
Categories
Funding
- Natural Science Foundation of Jiangsu Province [BK20180280]
- Innovation and Entrepreneurship Foundation of Jiangsu Province for Doctor [JSSCBS20211612]
- Science and Technology Development Foundation for Health of Nanjing [YKK20200]
- Nanjing Medical University [JNYYZXKY202021, JNYYRC202101]
- Scientific Research Foundation of the Affiliated Jiangning Hospital
- Social Development Foundation of Zhenjiang [SH2016045]
- Youth Innovation Foundation of the Affiliated Jiangning Hospital
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The study found that 2Ig mRNA and total B7-H3 membrane protein in AML may have potential diagnostic value, with high expression indicating worse overall survival. The expression of 4Ig and 2Ig was found to be methylation-independent in AML.
4IgB7-H3 (4Ig) and 2IgB7-H3 (2Ig) expression characteristics in acute myeloid leukemia (AML) remain unknown. This study investigated mRNA and membrane protein expression of two B7-H3 isoforms in AML cell lines and de novo patients by using RT-PCR and flow cytometry, and analyzed the B7-H3 promoter methylation state by utilizing RQ-MSP. 4Ig was the dominant isoform. 2Ig mRNA expression rate and abundance were elevated in AML in comparison with controls (P = 0.000 and 0.000), while no significant difference in 4Ig (P = 0.802, P = 0.398). Membrane protein levels of B7-H3 isoforms in AML was higher than controls, detected by total B7-H3 expression rate (P = 0.002), total B7-H3 mean fluorescence intensity (MFI) ratio of blast cells and lymphocytes (MFI ratio) (P = 0.000), and 4Ig B7-H3 MFI ratio (P = 0.005). Compared with 2Ig (low) group, 2Ig (high) patients had older age, lower NPM1 mutation, higher FLT3-ITD mutation, and declining complete remission (CR) rates (P = 0.026, 0.012, 0.047, and 0.028). In B7-H3 (high) group, there was a trend toward older age, M4 and M5, worse karyotype, and lower CR rates, although with no marked difference (P > 0.05). The overall survival (OS) of 2Ig (high) and B7-H3 (high) groups were shorter than that of 2Ig (low) and B7-H3 (low) groups in the whole and non-M3 AML cohorts (P = 0.006 and 0.046; P = 0.003 and 0.032). Besides, an unmethylated B7-H3 promoter was identified. In conclusion, 2Ig mRNA and total B7-H3 membrane protein tended to have potential diagnostic value for AML. Specifically, high 2Ig mRNA and total B7-H3 membrane protein expression indicate worse OS. 4Ig and 2Ig expression are methylation-independent.
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