Increased expression of CD70 in relapsed acute myeloid leukemia after hypomethylating agents.

IF 3.4 3区医学 Q1 PATHOLOGY Virchows Archiv Pub Date : 2024-11-01 Epub Date: 2024-02-22 DOI:10.1007/s00428-024-03741-8

Mario L Marques-Piubelli, Bijender Kumar, Rafet Basar, Siler Panowski, Surabhi Srinivasan, Kevin Norwood, Sacha Prashad, Victoria Szenes, Arun Balakumaran, Akanksha Arandhya, Wei Lu, Khaja Khan, Daniela Duenas, Salome McAllen, Javier A Gomez, Jared K Burks, Sunil Acharyal, Gautam Borthakur, Wei-Lien Wang, Wei Wang, Sa Wang, Luisa M Solis, David Marin, Katayoun Rezvani, May Daher, Francisco Vega

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Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, such as immunohistochemistry and flow cytometry, to investigate the expression of CD70 in bone marrow samples from treatment-naïve and relapsed AML patients after hypomethylating agents (HMA). Also, we evaluated the impact of HMA on CD70 expression and examined CD70 expression in various leukemic cell subsets and normal hematopoietic progenitors.

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使用低甲基化药物后复发的急性髓性白血病中 CD70 的表达增加。

急性髓性白血病（AML）是成人中最常见的急性白血病。虽然诱导化疗可使大多数患者病情缓解，但仍有相当一部分患者会复发。因此，需要新型疗法来提高复发和难治性急性髓细胞白血病患者的缓解率。CD70 是 CD27（TNF 超家族成员）的天然配体，似乎是一个很有前景的治疗靶点。因此，人们对开发能特异性靶向包括急性髓细胞性白血病在内的各种肿瘤的 CD70 的嵌合抗原受体（CAR）T 细胞疗法产品产生了浓厚的兴趣。在本研究中，我们采用免疫组化和流式细胞术等常规诊断技术，研究了低甲基化药物（HMA）治疗后的急性髓细胞白血病新发和复发患者骨髓样本中 CD70 的表达情况。此外，我们还评估了 HMA 对 CD70 表达的影响，并检测了各种白血病细胞亚群和正常造血祖细胞中 CD70 的表达。

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

Virchows Archiv 医学-病理学

CiteScore

7.40

自引率

2.90%

发文量

204

审稿时长

4-8 weeks

期刊介绍： Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.