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      Low IL7R Expression at Diagnosis Predicted Relapse in Adult Acute Myeloid Leukemia Patients With t(8;21)

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          Abstract

          Background

          Acute myeloid leukemia (AML) with t(8;21) needs to be further stratified. In addition to leukemia cells, immune cells in tumor microenvironment participate in tumor initiation, growth and progression. Interleukins (ILs)/interleukin receptors (ILRs) interaction plays important roles in the antitumor immune response. IL7R is reported to be relevant to prognosis in solid tumor and acute lymphoblastic leukemia. However, the prognostic significance of IL7R in t(8;21) AML remains to be clarified.

          Methods

          Bone marrows collected from 156 newly diagnosed t(8;21) AML patients were used for testing IL7R transcript level by TaqMan-based real-time quantitative PCR (RQ-PCR), and RNAseq were performed in 15 of them. Moreover, IL7R expression at diagnosis were measured by RQ-PCR and flow cytometry (FCM) simultaneously in other 13 t(8;21) AML patients.

          Results

          t(8;21) AML patients had varied IL7R transcript levels and were categorized into low-expression (IL7R-L) and high-expression (IL7R-H) groups; IL7R-L was significantly associated with a lower relapse-free survival (RFS) rate ( P=0.0027) and KIT D816/D820 mutation ( P=0.0010). Furthermore, IL7R-L was associated with a lower RFS rate in KIT D816/D820 group ( P=0.013) and IL7R-H/KIT D816/D820 patients had similar RFS to KIT N822/e8/WT patients ( P=0.35). GO analysis enrichment showed that down-regulated genes were predominantly involved in the regulation of T cell and leukocyte activation, proliferation and differentiation in IL7R-L group. IL7R-L had significantly lower levels of Granzymes A/B, CCR7, CD28 and CD27 than IL7R-H group (all P<0.05). FCM analysis showed IL7R protein was primarily expressed in CD4 + T and CD8 + T cell subset. A significant association was found between the transcript level of IL7R and the percentage of CD8 + T cells in nucleated cells ( P=0.015) but not CD4 + T cells ( P=0.47).

          Conclusion

          Low IL7R transcript level of bone marrow at diagnosis predicted relapse in t(8;21) AML, which might be caused by the difference in the amount, status and function of T cells.

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          Most cited references48

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                07 July 2022
                2022
                : 13
                : 909104
                Affiliations
                [1] Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease , Beijing, China
                Author notes

                Edited by: Tomasz Szczepanski, Medical University of Silesia, Poland

                Reviewed by: Szymon Skoczen, Jagiellonian University Medical College, Poland; Jacek Wachowiak, Poznan University of Medical Sciences, Poland

                *Correspondence: Ya-Zhen Qin, qin2000@ 123456aliyun.com

                This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.909104
                9302488
                35874754
                42af499b-e766-411b-9358-19d1a14a9d38
                Copyright © 2022 Xu, Sun, Wang, Chen, Wang, Li, Wang, Hao, Chang, Liu, Huang and Qin

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 March 2022
                : 06 June 2022
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 48, Pages: 10, Words: 4447
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Categories
                Immunology
                Original Research

                Immunology
                t(8;21) aml,il7r,relapse,real-time quantitative pcr,rnaseq,flow cytometry
                Immunology
                t(8;21) aml, il7r, relapse, real-time quantitative pcr, rnaseq, flow cytometry

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