Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia
B7-H3 isoforms, 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 isoforms in AML cell lines and de novo patients by using RT-PCR and flow cytometry, and analyzed the B7-H3...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Taylor & Francis Group
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/d8c8d09eae8f4426a9cd63794b646a46 |
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| Sumario: | B7-H3 isoforms, 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 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 B7-H3 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 2Iglow group, 2Ighigh 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-H3high group, there was a trend towards older age, –M4 and M5, worse karyotype, and lower CR rates, although with no marked difference (P>0.05). The overall survival (OS) of 2Ighigh and B7-H3high groups were shorter than that of 2Iglow and B7-H3low 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 isoforms membrane protein tended to have potential diagnostic value for AML. Specifically, high 2Ig mRNA expression and total B7-H3 membrane protein expression indicate worse OS. 4Ig and 2Ig expression are methylation-independent. |
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