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GRP78 和 CXCR4 的细胞表面表达与儿童高危急性淋巴细胞白血病的诊断有关。

Cell surface expression of GRP78 and CXCR4 is associated with childhood high-risk acute lymphoblastic leukemia at diagnostics.

机构信息

Unidad Universitaria de Investigación, División de Investigación, Facultad de Medicina, UNAM-Hospital Infantil de México Federico Gómez, Universidad 3000, CP 04510, Mexico City, Mexico.

Programa de Maestría y Doctorado en Ciencias Médicas Odontológicas y de la Salud, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.

出版信息

Sci Rep. 2022 Feb 11;12(1):2322. doi: 10.1038/s41598-022-05857-w.

DOI:10.1038/s41598-022-05857-w
PMID:35149705
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8837614/
Abstract

Acute lymphocytic leukemia is the most common type of cancer in pediatric individuals. Glucose regulated protein (GRP78) is an endoplasmic reticulum chaperone that facilitates the folding and assembly of proteins and regulates the unfolded protein response pathway. GRP78 has a role in survival of cancer and metastasis and cell-surface associated GRP78 (sGRP78) is expressed on cancer cells but not in normal cells. Here, we explored the presence of sGRP78 in pediatric B-ALL at diagnosis and investigated the correlation with bona fide markers of leukemia. By using a combination of flow cytometry and high multidimensional analysis, we found a distinctive cluster containing high levels of sGRP78, CD10, CD19, and CXCR4 in bone marrow samples obtained from High-risk leukemia patients, which was absent in the compartment of Standard-risk leukemia. We confirmed that sGRP78CXCR4 blood-derived cells were more frequent in High-risk leukemia patients. Finally, we analyzed the dissemination capacity of sGRP78 leukemia cells in a model of xenotransplantation. sGRP78 cells emigrated to the bone marrow and lymph nodes, maintaining the expression of CXCR4. Testing the presence of sGRP78 and CXCR4 together with conventional markers may help to achieve a better categorization of High and Standard-risk pediatric leukemia at diagnosis.

摘要

急性淋巴细胞白血病是儿科人群中最常见的癌症类型。葡萄糖调节蛋白 (GRP78) 是内质网伴侣，可促进蛋白质的折叠和组装，并调节未折叠蛋白反应途径。GRP78 在癌症的存活和转移中起作用，并且细胞表面相关的 GRP78（sGRP78）在癌细胞上表达，但在正常细胞上不表达。在这里，我们在儿科 B-ALL 诊断时探索了 sGRP78 的存在，并研究了其与真正的白血病标志物的相关性。通过结合流式细胞术和多维高分析，我们在高危白血病患者的骨髓样本中发现了一个独特的簇，其中包含高水平的 sGRP78、CD10、CD19 和 CXCR4，而在标准风险白血病的隔室中则不存在。我们证实，高危白血病患者中 sGRP78CXCR4 血液衍生细胞更为频繁。最后，我们在异种移植模型中分析了 sGRP78 白血病细胞的扩散能力。sGRP78 细胞迁移到骨髓和淋巴结，维持 CXCR4 的表达。同时检测 sGRP78 和 CXCR4 的存在与传统标志物一起可能有助于在诊断时更好地对高危和标准风险儿科白血病进行分类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/e5de2fa88fd9/41598_2022_5857_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/64083d24ea10/41598_2022_5857_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/5ee61fe14cfc/41598_2022_5857_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/2abed4734fb2/41598_2022_5857_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/0ee25bd7e14c/41598_2022_5857_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/e5de2fa88fd9/41598_2022_5857_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/64083d24ea10/41598_2022_5857_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/5ee61fe14cfc/41598_2022_5857_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/2abed4734fb2/41598_2022_5857_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/0ee25bd7e14c/41598_2022_5857_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc51/8837614/e5de2fa88fd9/41598_2022_5857_Fig5_HTML.jpg

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