Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia

Abstract

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.