Transcriptome Analysis Reveals the Induction of Apoptosis-Related Genes by a Monoclonal Antibody against a New Epitope of CD99 on T-Acute Lymphoblastic Leukemia

IF 3 Q3 IMMUNOLOGY

Antibodies Pub Date : 2024-05-17 DOI:10.3390/antib13020042

Nuchjira Takheaw, Kamonporn Kotemul, R. Chaiwut, S. Pata, Witida Laopajon, K. Rangnoi, M. Yamabhai, W. Kasinrerk

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引用次数: 0

Abstract

CD99 was demonstrated to be a potential target for antibody therapy on T-acute lymphoblastic leukemia (T-ALL). The ligation of CD99 by certain monoclonal antibodies (mAbs) induced T-ALL apoptosis. However, the molecular basis contributing to the apoptosis of T-ALL upon anti-CD99 mAb engagement remains elusive. In this study, using our generated anti-CD99 mAb clone MT99/3 (mAb MT99/3), mAb MT99/3 engagement strongly induced apoptosis of T-ALL cell lines, but not in non-malignant peripheral blood cells. By transcriptome analysis, upon mAb MT99/3 ligation, 13 apoptosis-related genes, including FOS, TNF, FASLG, BCL2A1, JUNB, SOCS1, IL27RA, PTPN6, PDGFA, NR4A1, SGK1, LPAR5 and LTB, were significantly upregulated. The epitope of CD99 recognized by mAb MT99/3 was then identified as the VDGENDDPRPP at residues 60–70 of CD99, which has never been reported. To the best of our knowledge, this is the first transcriptome data conducted in T-ALL with anti-CD99 mAb engagement. These findings provide new insights into CD99 implicated in the apoptosis of T-ALL. The identification of a new epitope and apoptosis-related genes that relate to the induction of apoptosis by mAb MT99/3 may serve as a new therapeutic target for T-ALL. The anti-CD99 mAb clone MT99/3 might be a candidate for further development of a therapeutic antibody for T-ALL therapy.

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转录组分析揭示了针对 T 型急性淋巴细胞白血病 CD99 新表位的单克隆抗体对凋亡相关基因的诱导作用

CD99被证明是T-急性淋巴细胞白血病（T-ALL）抗体疗法的潜在靶点。某些单克隆抗体（mAbs）与 CD99 连接可诱导 T-ALL 细胞凋亡。然而，抗 CD99 mAb 参与 T-ALL 细胞凋亡的分子基础仍未确定。在这项研究中，利用我们生成的抗 CD99 mAb 克隆 MT99/3（mAb MT99/3），mAb MT99/3 参与可强烈诱导 T-ALL 细胞系凋亡，但在非恶性外周血细胞中却没有诱导作用。通过转录组分析，mAb MT99/3连接后，13个与凋亡相关的基因，包括FOS、TNF、FASLG、BCL2A1、JUNB、SOCS1、IL27RA、PTPN6、PDGFA、NR4A1、SGK1、LPAR5和LTB显著上调。mAb MT99/3 识别的 CD99 表位被确定为 CD99 第 60-70 位残基上的 VDGENDDPRPP，而这一表位从未被报道过。据我们所知，这是首次在抗 CD99 mAb 参与的 T-ALL 中进行转录组数据分析。这些发现为了解 CD99 与 T-ALL 细胞凋亡的关系提供了新的视角。与 mAb MT99/3 诱导细胞凋亡有关的新表位和细胞凋亡相关基因的鉴定可作为 T-ALL 的新治疗靶点。抗CD99 mAb克隆MT99/3可能是进一步开发治疗T-ALL的候选抗体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antibodies IMMUNOLOGY-

CiteScore

7.10

自引率

6.40%

发文量

审稿时长

11 weeks

期刊介绍： Antibodies (ISSN 2073-4468), an international, peer-reviewed open access journal which provides an advanced forum for studies related to antibodies and antigens. It publishes reviews, research articles, communications and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided. Electronic files or software regarding the full details of the calculation and experimental procedure - if unable to be published in a normal way - can be deposited as supplementary material. This journal covers all topics related to antibodies and antigens, topics of interest include (but are not limited to): antibody-producing cells (including B cells), antibody structure and function, antibody-antigen interactions, Fc receptors, antibody manufacturing antibody engineering, antibody therapy, immunoassays, antibody diagnosis, tissue antigens, exogenous antigens, endogenous antigens, autoantigens, monoclonal antibodies, natural antibodies, humoral immune responses, immunoregulatory molecules.