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:	Wei Zhang, Lingyi Zhang, Jun Qian, Jiang Lin, Qiaoyun Chen, Qian Yuan, Jingdong Zhou, Tingjuan Zhang, Jinning Shi, Hong Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	4ig b7-h3 2ig b7-h3 acute myeloid leukemia prognosis Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/d8c8d09eae8f4426a9cd63794b646a46
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spelling	oai:doaj.org-article:d8c8d09eae8f4426a9cd63794b646a462021-11-26T11:19:49ZExpression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia2165-59792165-598710.1080/21655979.2021.2001182https://doaj.org/article/d8c8d09eae8f4426a9cd63794b646a462021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2001182https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987B7-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.Wei ZhangLingyi ZhangJun QianJiang LinQiaoyun ChenQian YuanJingdong ZhouTingjuan ZhangJinning ShiHong ZhouTaylor & Francis Grouparticle4ig b7-h32ig b7-h3acute myeloid leukemiaprognosisBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	4ig b7-h3 2ig b7-h3 acute myeloid leukemia prognosis Biotechnology TP248.13-248.65
spellingShingle	4ig b7-h3 2ig b7-h3 acute myeloid leukemia prognosis Biotechnology TP248.13-248.65 Wei Zhang Lingyi Zhang Jun Qian Jiang Lin Qiaoyun Chen Qian Yuan Jingdong Zhou Tingjuan Zhang Jinning Shi Hong Zhou Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia
description	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.
format	article
author	Wei Zhang Lingyi Zhang Jun Qian Jiang Lin Qiaoyun Chen Qian Yuan Jingdong Zhou Tingjuan Zhang Jinning Shi Hong Zhou
author_facet	Wei Zhang Lingyi Zhang Jun Qian Jiang Lin Qiaoyun Chen Qian Yuan Jingdong Zhou Tingjuan Zhang Jinning Shi Hong Zhou
author_sort	Wei Zhang
title	Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia
title_short	Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia
title_full	Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia
title_fullStr	Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia
title_full_unstemmed	Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia
title_sort	expression characteristic of 4ig b7-h3 and 2ig b7-h3 in acute myeloid leukemia
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/d8c8d09eae8f4426a9cd63794b646a46
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Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia

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