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慢性粒细胞白血病中融合基因的患病率及树突状细胞的T细胞刺激能力

Prevalence of the fusion gene and T cell stimulation capacity of dendritic cells in chronic myelogenous leukemia.

作者信息

Gaafar Ameera, Al-Omar Hamad M, Manogaran Pulicat S, Almohareb Fahad, Alhussein Khalid

机构信息

Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Center Riyadh 11211, Saudi Arabia.

Section of Adult Hematology/HSCT, Oncology Center, King Faisal Specialist Hospital and Research Center Riyadh 11211, Saudi Arabia.

出版信息

Am J Transl Res. 2023 Feb 15;15(2):967-981. eCollection 2023.

Abstract

Dendritic cell (DC) vaccines are promising for immunotherapy, and their production using CD34 hematopoietic stem cells (HPSCs) from patients with chronic myelogenous leukemia (CML) and healthy donors is well established. However, the generation of CD1aCD14 DCs and their functional properties in patients with CML remain elusive. Here, we aimed to study the biology of DCs generated from CD34 HPSCs and evaluate the status of their BCR/ABL translocation, ability to stimulate T cells, and capacity of endocytosis compared to DCs derived from CD34 HPSCs from both patients with CML and healthy donors. CD1aCD14 DCs were generated from CD34 HPSCs and evaluated morphologically and functionally. CD34 cells are frequently selected for transplantation and the entire CD34 HPSC fraction is wasted. Here, we anticipated the CD34 HPSC subset to constitute an invaluable source for acquiring DCs for immunotherapy. CD34 and CD34 HPSCs were sorted from the bone marrow samples of CML patients and healthy donors and differentiated in a similar way. DCs from CD34Lin and CD34Lin HPSCs expressed comparable surface markers (CD80, CD83, CD86, HLA-DR, CD40, and CD54). Functional analysis revealed that DCs acquired from both subsets retained a potent allogeneic T cell stimulatory capacity and an efficient phagocytic ability and showed a similar translocation status. In conclusion, DCs were successfully differentiated from the CD34Lin cell subset and showed potent functional capacities, indicating their potential for application in immunotherapy and basic research.

摘要

树突状细胞(DC)疫苗在免疫治疗方面前景广阔,利用慢性粒细胞白血病(CML)患者和健康供体的CD34造血干细胞(HPSC)生产DC疫苗的方法已得到充分确立。然而,CML患者中CD1aCD14 DC的生成及其功能特性仍不清楚。在此,我们旨在研究从CD34 HPSC生成的DC的生物学特性,并与CML患者和健康供体的CD34 HPSC衍生的DC相比,评估其BCR/ABL易位状态、刺激T细胞的能力和内吞能力。从CD34 HPSC生成CD1aCD14 DC,并对其进行形态学和功能评估。CD34细胞经常被选用于移植,而整个CD34 HPSC部分被浪费了。在此,我们预期CD34 HPSC亚群将成为获取用于免疫治疗的DC的宝贵来源。从CML患者和健康供体的骨髓样本中筛选出CD34和CD34 HPSC,并以类似的方式进行分化。来自CD34Lin和CD34Lin HPSC的DC表达了相当的表面标志物(CD80、CD83、CD86、HLA-DR、CD40和CD54)。功能分析表明,从两个亚群获得的DC都保留了强大的同种异体T细胞刺激能力和高效的吞噬能力,并显示出相似的易位状态。总之,DC已成功地从CD34Lin细胞亚群中分化出来,并显示出强大的功能能力,表明它们在免疫治疗和基础研究中的应用潜力。

相似文献

本文引用的文献

1
Chronic myeloid leukaemia.慢性髓性白血病。
Lancet. 2021 Nov 20;398(10314):1914-1926. doi: 10.1016/S0140-6736(21)01204-6. Epub 2021 Aug 20.
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Advances in immunotherapy for acute myeloid leukemia.急性髓系白血病的免疫疗法进展。
Future Oncol. 2018 Apr;14(10):963-978. doi: 10.2217/fon-2017-0459. Epub 2018 Mar 15.

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