Expression characteristic of <i>4Ig B7-H3</i> and <i>2Ig B7-H3</i> in acute myeloid leukemia

Abstract

<i>4IgB7-H3</i> (<i>4Ig</i>) and <i>2IgB7-H3</i> (<i>2Ig</i>) expression characteristics in acute myeloid leukemia (AML) remain unknown. This study investigated mRNA and membrane protein expression of two <i>B7-H3</i> isoforms in AML cell lines and de novo patients by using RT-PCR and flow cytometry, and analyzed the <i>B7-H3</i> promoter methylation state by utilizing RQ-MSP. <i>4Ig</i> was the dominant isoform. <i>2Ig</i> mRNA expression rate and abundance were elevated in AML in comparison with controls (<i>P</i> = 0.000 and 0.000), while no significant difference in <i>4Ig</i> (<i>P</i> = 0.802, <i>P</i> = 0.398). Membrane protein levels of <i>B7-H3</i> isoforms in AML was higher than controls, detected by total <i>B7-H3</i> expression rate (<i>P</i> = 0.002), total <i>B7-H3</i> mean fluorescence intensity (MFI) ratio of blast cells and lymphocytes (MFI ratio) (<i>P</i> = 0.000), and <i>4Ig B7-H3</i> MFI ratio (<i>P</i> = 0.005). Compared with <i>2Ig</i>^low group, <i>2Ig</i>^high patients had older age, lower <i>NPM1</i> mutation, higher <i>FLT3-ITD</i> mutation, and declining complete remission (CR) rates (<i>P</i> = 0.026, 0.012, 0.047, and 0.028). In <i>B7-H3</i>^high group, there was a trend toward older age, M4 and M5, worse karyotype, and lower CR rates, although with no marked difference (<i>P</i> > 0.05). The overall survival (OS) of <i>2Ig</i>^high and <i>B7-H3</i>^high groups were shorter than that of <i>2Ig</i>^low and <i>B7-H3</i>^low groups in the whole and non-M3 AML cohorts (<i>P</i> = 0.006 and 0.046; <i>P</i> = 0.003 and 0.032). Besides, an unmethylated <i>B7-H3</i> promoter was identified. In conclusion, <i>2Ig</i> mRNA and total <i>B7-H3</i> membrane protein tended to have potential diagnostic value for AML. Specifically, high <i>2Ig</i> mRNA and total <i>B7-H3</i> membrane protein expression indicate worse OS. <i>4Ig</i> and <i>2Ig</i> expression are methylation-independent.