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慢性淋巴细胞白血病（CLL）肿瘤B细胞与间充质基质细胞（MSC）之间的相互作用：对肿瘤细胞存活的影响

Cross-talk between chronic lymphocytic leukemia (CLL) tumor B cells and mesenchymal stromal cells (MSCs): implications for neoplastic cell survival.

作者信息

Trimarco Valentina, Ave Elisa, Facco Monica, Chiodin Giorgia, Frezzato Federica, Martini Veronica, Gattazzo Cristina, Lessi Federica, Giorgi Carlo Alberto, Visentin Andrea, Castelli Monica, Severin Filippo, Zambello Renato, Piazza Francesco, Semenzato Gianpietro, Trentin Livio

机构信息

Padua University School of Medicine, Department of Medicine, Hematology and Clinical Immunology Branch, Padua, Italy.

Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.

出版信息

Oncotarget. 2015 Dec 8;6(39):42130-49. doi: 10.18632/oncotarget.6239.

DOI:10.18632/oncotarget.6239
PMID:26517523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4747215/
Abstract

Leukemic cells from Chronic Lymphocytic Leukemia (CLL) patients interact with stromal cells of the surrounding microenvironment. Mesenchymal Stromal Cells (MSCs) represent the main population in CLL marrow stroma, which may play a key role for disease support and progression. In this study we evaluated whether MSCs influence in vitro CLL cell survival. MSCs were isolated from the bone marrow of 46 CLL patients and were characterized by flow cytometry analysis. Following co-culture of MSCs and leukemic B cells, we demonstrated that MSCs were able to improve leukemic B cell viability, this latter being differently dependent from the signals coming from MSCs. In addition, we found that the co-culture of MSCs with leukemic B cells induced an increased production of IL-8, CCL4, CCL11, and CXCL10 chemokines.As far as drug resistance is concerned, MSCs counteract the cytotoxic effect of Fludarabine/Cyclophosphamide administration in vivo, whereas they do not protect CLL cells from the apoptosis induced by the kinase inhibitors Bafetinib and Ibrutinib. The evidence that leukemic clones are conditioned by environmental stimuli suggest new putative targets for therapy in CLL patients.

摘要

慢性淋巴细胞白血病（CLL）患者的白血病细胞与周围微环境中的基质细胞相互作用。间充质基质细胞（MSC）是CLL骨髓基质中的主要细胞群，可能在疾病支持和进展中起关键作用。在本研究中，我们评估了MSC是否影响体外CLL细胞的存活。从46例CLL患者的骨髓中分离出MSC，并通过流式细胞术分析进行表征。在MSC与白血病B细胞共培养后，我们证明MSC能够提高白血病B细胞的活力，而白血病B细胞的活力对来自MSC的信号有不同程度的依赖性。此外，我们发现MSC与白血病B细胞共培养可诱导IL-8、CCL4、CCL11和CXCL10趋化因子的产生增加。就耐药性而言，MSC可抵消体内氟达拉滨/环磷酰胺给药的细胞毒性作用，而它们不能保护CLL细胞免受激酶抑制剂巴非替尼和依鲁替尼诱导的凋亡。白血病克隆受环境刺激影响的证据提示了CLL患者治疗的新潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/0ede3f74e617/oncotarget-06-42130-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/6a72252423e3/oncotarget-06-42130-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/0ede3f74e617/oncotarget-06-42130-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/768d9c7e27ce/oncotarget-06-42130-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/e0001229072b/oncotarget-06-42130-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/38891a4f9d7c/oncotarget-06-42130-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/43a3695066de/oncotarget-06-42130-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/8c8ba0277704/oncotarget-06-42130-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/ed790ec9333c/oncotarget-06-42130-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/9521906fac49/oncotarget-06-42130-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/6a72252423e3/oncotarget-06-42130-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e6/4747215/0ede3f74e617/oncotarget-06-42130-g009.jpg

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本文引用的文献

1
Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46(2):219-234.赖·KR、萨维茨基·A、克朗凯特·EP、查纳纳·AD、利维·RN、帕斯特纳克·BS。慢性淋巴细胞白血病的临床分期。《血液》。1975年；46(2):219 - 234。
Blood. 2016 Oct 27;128(17):2109. doi: 10.1182/blood-2016-08-737650.
2
Chronic Lymphocytic Leukemia: Current Concepts.慢性淋巴细胞白血病：当前概念
Anticancer Res. 2015 Oct;35(10):5149-65.
3
The B-cell receptor pathway: a critical component of healthy and malignant immune biology.
Int J Mol Sci. 2024 Feb 21;25(5):2527. doi: 10.3390/ijms25052527.
4
Enhanced Costimulatory Signaling Improves CAR T-cell Effector Responses in CLL.增强共刺激信号可改善 CLL 中 CAR T 细胞的效应器反应。
Cancer Res Commun. 2022 Sep 30;2(9):1089-1103. doi: 10.1158/2767-9764.CRC-22-0200. eCollection 2022 Sep.
5
Mesenchymal stromal cell senescence in haematological malignancies.血液系统恶性肿瘤中的间充质基质细胞衰老
Cancer Metastasis Rev. 2023 Mar;42(1):277-296. doi: 10.1007/s10555-022-10069-9. Epub 2023 Jan 9.
6
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Cell Death Dis. 2022 Oct 8;13(10):860. doi: 10.1038/s41419-022-05287-6.
7
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9
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10
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4
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5
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6
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PLoS One. 2012;7(6):e39902. doi: 10.1371/journal.pone.0039902. Epub 2012 Jun 29.
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Leuk Lymphoma. 2012 Sep;53(9):1735-42. doi: 10.3109/10428194.2012.666662.