CXC趋化因子受体1/2在急性白血病中的异常表达及临床意义探析

刘彦权; 曾敏娟; 殷悦; 沈建箴; 唐焕文

doi:10.3969/j.issn.2095-5227.2023.03.002

CXC趋化因子受体1/2在急性白血病中的异常表达及临床意义探析

doi: 10.3969/j.issn.2095-5227.2023.03.002

1.
广东医科大学第一临床医学院血液内科，广东东莞　523808
2.
广东医科大学基础医学院解剖学教研室，广东东莞　523808
3.
福建省血液病研究所，福建医科大学附属协和医院血液科，福建福州　350001

基金项目: 国家自然科学基金面上项目(82073582)；广东省教育厅高校特色创新项目(2020KTSCX048)；广东医科大学学科建设项目(4SG22003G；4SG21209G)；广东医科大学科技创新专项计划项目(4SG22046G)

详细信息

作者简介:
刘彦权，男，博士，主治医师，讲师。研究方向：血液肿瘤与罕见病的科研、临床及高等医学教育研究。Email: doctorliuyanquan@163.com

通讯作者:
唐焕文，男，博士，教授，院长，博士生导师。Email: thw@gdmu.edu.cn

中图分类号: R733.71
计量
- 文章访问数: 46
- HTML全文浏览量: 35
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2022-07-03
- 网络出版日期: 2023-02-14
- 刊出日期: 2023-03-28

Abnormal expression and clinical significance of CXC chemokine receptor 1/2 in acute leukemia

1.
Department of Hematology, the First Clinical Medical College of Guangdong Medical University, Dongguan 523808, Guangdong Province, China
2.
Department of Anatomy, School of Basic Medicine, Guangdong Medical University, Dongguan 523808, Guangdong Province, China
3.
Fujian Institute of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China

More Information

Corresponding author: TANG Huanwen. Email: thw@gdmu.edu.cn

摘要

摘要: 背景 CXCR家族已成为恶性肿瘤领域的研究热点，积极寻找并探究与急性白血病(acute leukemia，AL)发生、发展及预后相关的CXCR家族成员，在抗白血病基础研究与临床诊疗中具有重要意义。目的探索骨髓微环境中CXC趋化因子受体1/2(CXC chemokine receptor 1/2，CXCR1/2)在AL患者骨髓单个核细胞中的表达水平及其与AL患者临床特征、疗效及预后的关系，为寻找AL的治疗靶点和病情监测提供新方向。方法收集2018年11月- 2020年12月福建医科大学附属协和医院86例初诊(new-diagnosed，ND) AL患者骨髓标本同时收集26例健康者标本，其中男性17例，女性9例，中位年龄36.5(范围：23 ~ 49)岁。采用qRT-PCR技术检测两组人群骨髓单个核细胞中CXCR1/2表达。以CXCR1/2中位表达水平(Expression_median)作为界值，将ND-AL患者分为CXCR1/2高表达组和低表达组，分析不同CXCR1/2表达水平与AL患者临床特征及指标之间的关系和临床意义。结果 86例ND-AL患者中，包括29例急性淋巴细胞白血病(acute lymphoblastic leukemia，ALL)患者和57例急性髓系白血病(acute myeloid leukemia，AML)患者。AL组中CXCR1[Md(IQR): 0.691(0.176 ~ 2.14) vs 0.278(0.088 ~ 0.613)， P＜0.05]、CXCR2相对表达量[Md (IQR):1.938(0.729 ~ 3.681) vs 0.419(0.079 ~ 1.268)， P＜0.01]均高于健康对照组，AML组与ALL组的CXCR1/2相对表达量差异无统计学意义(P＞0.05)；CXCR1/2的高表达与AL不良临床特征和指标有关(P＜0.05)，易出现髓外浸润、复发难治等不良结局。结论 AL患者的CXCR1/2表达上调，其对于AL的病情监测有一定的参考价值。
- 白血病 /
- 髓样 /
- 急性 /
- CXC趋化因子受体1 /
- CXC趋化因子受体2 /
- 分子靶点 /
- 预后
Abstract: Background CXCR family has become a research hotspot in the field of malignant tumors. Actively searching and exploring CXCR family members that are closely related to the occurrence, development and prognosis of acute leukemia (AL) are of great practical significance in the basic research and clinical diagnosis and treatment of anti-leukemia. Objective To explore the expression level of CXC chemokine receptor 1/2 (CXCR1/2) under bone marrow microenvironment in bone marrow mononuclear cells of patients with AL, and analyze the relationship between CXCR1/2 expression and clinical characteristics, curative effect and prognosis of AL patients, so as to provide a new direction for the therapeutic target and disease monitoring of AL. Methods Bone marrow specimens from 86 newly-diagnosed (ND) AL patients from November 2018 to December 2020 in Fujian Medical University Union Hospital were collected, including 49 males and 37 females, with a median age of 48 years (range: 17-73 years); At the same time, 26 healthy samples were collected, including 17 males and 9 females, with a median age of 36.5 years (range: 23-49 years). And quantitative real-time polymerase chain reaction (qRT-PCR) technology was used to detect the expression level of CXCR1/2. Taking the median expression level of CXCR1/2 as the cut-off value, the ND-AL patients were divided into CXCR1/2 high expression group and low expression group, and the relationship between different CXCR1/2 expression levels and various clinical characteristics, indicators and clinical significance of AL patients were analyzed respectively. Results Among the 86 ND-AL patients included in this study, there were 29 patients with acute lymphoblastic leukemia (ALL) and 57 patients with acute myeloid leukemia (AML). The relative expression levels of CXCR1(Md[IQR]: 0.691 [0.176-2.140] vs 0.278 [0.088-0.613], P＜0.05) and CXCR2 (Md[IQR]: 1.938 [0.729-3.681] vs 0.419 [0.079-1.268], P＜0.01) in the AL group were higher than those in the healthy control group; there was no significant difference in the relative expression of CXCR1/2 between the AML group and the ALL group (P＞0.05). The high expression of CXCR1/2 was associated with adverse clinical features and indicators of AL (P＜0.05), and was prone to have adverse outcomes such as extramedullary infiltration, relapse and refractory. Conclusion CXCR1/2 is up-regulated in AL, which has important reference value for the disease detection of AL.
- leukemia /
- myeloid /
- acute /
- CXC chemokine receptor 1 /
- CXC chemokine receptor 2 /
- molecular targets /
- prognosis

HTML全文

图 1 CXCR1、CXCR2在初诊AL组(含分组)与健康对照组中的表达比较

Figure 1. Differences in the relative expression of CXCR1 and CXCR2 in newly diagnosed AL groups and healthy control group

下载: 全尺寸图片幻灯片

表 1 临床AL标本分型统计(例，%)

Table 1. Classification and statistics of clinical AL specimens (n, %)

分型	ALL (n=29)	AML (n=57)
T	7(24.14)
B	22(75.86)
M0		2(3.51)
M1		1(1.75)
M2		19(33.33)
M3		10(17.54)
M4		2(3.51)
M5		23(40.35)

下载: 导出CSV

表 2 AL患者CXCR1、CXCR2表达与临床特征的关系

Table 2. Relationship between CXCR1/2 expression and clinical characteristics in AL patients

指标	CXCR1		χ²/t/Z值	P值	CXCR2		χ²/t/Z值	P值
指标	CXCR1表达＜0.691 (n=37)	CXCR1表达 ≥0.691 (n=49)	χ²/t/Z值	P值	表达＜1.938 (n=34)	表达 ≥1.938 (n=52)	χ²/t/Z值	P值
性别(男/女)/例	21/16	28/21	0.001	0.971	19/15	30/22	0.027	0.868
年龄/[岁，Md(IQR)]	42.0(17.0，64.0)	51.0(26.0，73.0)	2.000	0.054	45.0(17.0，62.0)	57.0(23.0，73.0)	2.359	0.024
发热/(例，%)	17(45.95)	41(83.67)	13.666	＜0.001	15(44.12)	45(81.82)	17.539	＜0.001
疲惫/(例，%)	26(70.27)	37(75.51)	0.295	0.587	24(70.59)	47(85.45)	5.595	0.018
苍白/(例，%)	23(62.16)	46(93.88)	13.370	＜0.001	19(55.88)	51(92.73)	24.170	＜0.001
白细胞计数/(L^-1，× 10⁹)	12.64 ± 7.41	23.42 ± 6.25	7.309	＜0.001	16.53 ± 4.29	25.91 ± 6.47	8.084	＜0.001
血红蛋白/(g·L^-1)	83.41 ± 6.18	72.37 ± 9.47	6.525	＜0.001	79.46 ± 6.32	67.95 ± 8.24	6.918	＜0.001
血小板计数/(L^-1，× 10⁹)	77.21 ± 3.68	52.93 ± 7.14	20.474	＜0.001	74.79 ± 3.68	65.93 ± 7.62	7.198	＜0.001
乳酸脱氢酶/(U·L^-1)	397.43 ± 29.43	474.24 ± 64.17	7.410	＜0.001	406.43 ± 32.51	512.96 ± 43.95	12.897	＜0.001
C反应蛋白/(mg·L^-1)	32.94 ± 9.35	58.85 ± 16.38	9.255	＜0.001	29.94 ± 8.16	63.25 ± 12.93	14.645	＜0.001
降钙素原/[ng·mL^-1，Md(IQR)]	0.25(0.04，1.32)	0.38(0.03，2.29)	-0.370	0.712	0.21(0.03，1.04)	0.35(0.02，2.51)	-0.200	0.835
骨髓原始细胞数/%	49.42 ± 9.39	54.39 ± 6.77	2.728	0.008	52.46 ± 8.53	67.39 ± 5.19	9.158	＜0.001
外周血原始细胞数/%	41.23 ± 5.12	45.66 ± 7.61	3.222	0.002	43.23 ± 4.63	49.23 ± 6.89	4.830	＜0.001
肝脾大/(例，%)	12(32.43)	29(59.18)	6.048	0.014	11(32.35)	36(65.45)	11.281	0.001
淋巴结肿大/(例，%)	8(21.62)	15(30.61)	0.870	0.351	9(26.47)	23(41.82)	2.775	0.096

下载: 导出CSV

表 3 AML患者CXCR1、CXCR2表达与临床指标的关系

Table 3. Relationship between the expression of CXCR1, CXCR2 and clinical indicators in the AML patients

指标	CXCR1		χ²/t值	P值	CXCR2		χ²/t值	P值
指标	表达＜0.704 (n=24)	表达≥0.704 (n=33)	χ²/t值	P值	表达＜1.965 (n=22)	表达≥1.965 (n=35)	χ²/t值	P值
性别(男/女)/例	16/8	15/18	2.520	0.112	13/9	18/17	0.320	0.572
年龄/(例，%)			1.733	0.188			3.407	0.065
＜60岁	22(91.67)	26(78.79)			21(95.45)	27(77.14)
≥60岁	2(8.33)	7(21.21)			1(4.55)	8(22.86)
FAB分型/(例，%)			7.020	0.219			24.560	＜0.001
M0	0(0)	2(6.06)			1(4.55)	1(2.86)
M1	1(4.17)	0(0)			1(4.55)	0(0)
M2	6(25.00)	13(39.39)			11(50.00)	8(22.86)
M3	7(29.17)	3(9.09)			8(36.36)	2(5.71)
M4	1(4.17)	1(3.03)			0(0)	2(5.71)
M5	9(37.5)	14(42.42)			1(4.55)	22(62.86)
M6	0(0)	0(0)			0(0)	0(0)
M7	0(0)	0(0)			0(0)	0(0)
白细胞/(L^-1，× 10⁹)	11.73 ± 3.28	20.91 ± 5.92	7.470	＜0.001	15.46 ± 6.19	21.72 ± 4.87	4.251	＜0.001
血红蛋白/(g·L^-1)	81.62 ± 7.13	69.72 ± 4.95	7.036	＜0.001	85.53 ± 7.41	71.54 ± 6.39	7.564	＜0.001
血小板/(L^-1，× 10⁹)	83.49 ± 9.36	62.43 ± 6.87	9.805	＜0.001	66.74 ± 5.38	49.95 ± 5.06	11.903	＜0.001
骨髓原始细胞数/%	52.81 ± 6.92	65.83 ± 7.49	6.688	＜0.001	56.36 ± 8.53	67.61 ± 7.98	5.046	＜0.001
髓外浸润/(例，%)	5(20.83)	11(33.33)	1.075	0.300	4(18.18)	12(34.29)	1.735	0.188
核型/(例，%)			5.528	0.478			12.698	0.048
正常	11(45.83)	16(48.48)			7(31.81)	20(57.14)
复杂	1(4.17)	5(15.15)			1(4.55)	5(14.29)
t (15; 17)	7(29.17)	3(9.09)			8(36.36)	2(5.71)
t (8; 21)	1(4.17)	2(6.06)			2(9.09)	1(2.86)
inv (16)	1(4.17)	1(3.03)			1(4.54)	1(2.86)
t (9; 22)	1(4.17)	1(3.03)			0(0)	2(5.71)
数据缺失或其他	2(8.33)	5(15.15)			3(13.64)	4(11.43)
细胞遗传学/(例，%)			2.800	0.424			6.030	0.110
低危	9(37.5)	7(21.21)			10(45.45)	6(17.14)
中危	11(45.83)	15(45.45)			7(31.82)	19(54.29)
高危	2(8.33)	6(18.18)			2(9.09)	6(17.14)
数据缺失	2(8.33)	5(15.15)			3(13.64)	4(11.43)
突变基因/(例，%)			7.680	0.742			8.821	0.638
CEBPA (+)	7(29.16)	3(9.09)			6(27.27)	4(11.43)
FLT3-ITD (+)	5(20.83)	14(42.42)			5(22.73)	14(40.00)
NPM1 (+)	3(12.5)	5(15.15)			5(22.73)	3(8.57)
c-kit (+)	1(4.17)	3(9.09)			1(4.55)	3(8.57)
RUNX1 (+)	1(4.17)	4(12.12)			2(9.09)	3(8.57)
ASXL1 (+)	2(8.33)	5(15.15)			3(13.64)	4(11.43)
DNMT3A (+)	2(8.33)	4(12.12)			2(9.09)	4(11.43)
IDH1/2 (+)	2(8.33)	3(9.09)			3(13.64)	2(5.71)
NRAS or KRAS (+)	3(12.5)	8(24.24)			2(9.09)	9(25.71)
TET2 (+)	2(8.33)	5(15.15)			3(13.64)	4(11.43)
EZH2 (+)	1(4.17)	3(9.09)			1(4.55)	3(8.57)
数据缺失	2(8.33)	5(15.15)			3(13.64)	4(11.43)

下载: 导出CSV

参考文献(19)

[1]	刘彦权,周华蓉,付海英,等. 白血病的传统中医临床诊疗研究进展[J]. 中国医药指南,2020,18(12): 30-32.
[2]	闫飞,魏述宁,刘佳,等. 我国北方地区成人急性白血病发病的生活及环境危险因素分析[J]. 解放军医学院学报,2021,42(5): 488-493.
[3]	刘彦权,沈建箴. CXCR1与恶性肿瘤的相关性[J]. 国际肿瘤学杂志,2020,47(12): 732-736.
[4]	Ruffini PA. The CXCL8-CXCR1/2 axis as a therapeutic target in breast cancer stem-like cells[J]. Front Oncol,2019,9: 40. doi: 10.3389/fonc.2019.00040
[5]	Mishra A,Suman KH,Nair N,et al. An updated review on the role of the CXCL8-CXCR1/2 axis in the progression and metastasis of breast cancer[J]. Mol Biol Rep,2021,48(9): 6551-6561.
[6]	Han ZJ,Li YB,Yang LX,et al. Roles of the CXCL8-CXCR1/2 axis in the tumor microenvironment and immunotherapy[J]. Molecules,2021,27(1): 137.
[7]	Wang RX,Ji P,Gong Y,et al. Value of CXCL8-CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients:a retrospective pilot study[J]. Breast Cancer Res Treat,2020,181(3): 561-570.
[8]	Singh V,Uddin MH,Zonder JA,et al. Circular RNAs in acute myeloid leukemia[J]. Mol Cancer,2021,20(1): 149.
[9]	Lee JB,Vasic D,Kang H,et al. State-of-art of cellular therapy for acute leukemia[J]. Int J Mol Sci,2021,22(9): 4590.
[10]	IARC. Latest global cancer data: Cancer burden rises to 19.3 million new cases and 10.0 million cancer deaths in 2020. ［EB/OL］. https://www.iarc.who.int/fr/news-events/latest-global-cancer-data-cancer-burden-rises-to-19-3-million-new-cases-and-10-0-million-cancer-deaths-in-2020.
[11]	刘彦权,沈建箴,周华蓉. 血液肿瘤表观遗传调控及其靶向治疗研究进展[J]. 解放军医学院学报,2019,40(11): 1101-1105.
[12]	Nagarsheth N,Wicha MS,Zou WP. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy[J]. Nat Rev Immunol,2017,17(9): 559-572.
[13]	Hu LT,Deng WJ,Chu ZS,et al. Comprehensive analysis of CXCR family members in lung adenocarcinoma with prognostic values[J]. BMC Pulm Med,2022,22(1): 259.
[14]	He JR,Jiang ZZ,Lei JW,et al. Prognostic value and therapeutic perspectives of CXCR members in the glioma microenvironment[J]. Front Genet,2022,13: 787141. doi: 10.3389/fgene.2022.787141
[15]	Ha H,Debnath B,Neamati N. Role of the CXCL8-CXCR1/2 axis in cancer and inflammatory diseases[J]. Theranostics,2017,7(6): 1543-1588.
[16]	Che JX,Song R,Chen BH,et al. Targeting CXCR1/2:the medicinal potential as cancer immunotherapy agents,antagonists research highlights and challenges ahead[J]. Eur J Med Chem,2020,185: 111853. doi: 10.1016/j.ejmech.2019.111853
[17]	Liu Q,Li AP,Tian YJ,et al. The CXCL8-CXCR1/2 pathways in cancer[J]. Cytokine Growth Factor Rev,2016,31: 61-71. doi: 10.1016/j.cytogfr.2016.08.002
[18]	Wu S,Saxena S,Varney ML,et al. CXCR1/2 chemokine network regulates melanoma resistance to chemotherapies mediated by NF-κB[J]. Curr Mol Med,2017,17(6): 436-449.
[19]	Tang W, Li ZY, Li X, et al. High CXCR2 expression predicts poor prognosis in adult patients with acute myeloid leukemia［J］. Ther Adv Hematol, 2020, 11: 2040620720958586.

施引文献

资源附件(0)

访问统计

点击查看大图

图(1) / 表(3)

计量

文章访问数: 46
HTML全文浏览量: 35
PDF下载量: 1
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

CXC趋化因子受体1/2在急性白血病中的异常表达及临床意义探析

doi: 10.3969/j.issn.2095-5227.2023.03.002

作者简介:
刘彦权，男，博士，主治医师，讲师。研究方向：血液肿瘤与罕见病的科研、临床及高等医学教育研究。Email: doctorliuyanquan@163.com

通讯作者:
唐焕文，男，博士，教授，院长，博士生导师。Email: thw@gdmu.edu.cn

计量

Abnormal expression and clinical significance of CXC chemokine receptor 1/2 in acute leukemia

Corresponding author: TANG Huanwen. Email: thw@gdmu.edu.cn

计量

目录

留言板

CXC趋化因子受体1/2在急性白血病中的异常表达及临床意义探析

doi: 10.3969/j.issn.2095-5227.2023.03.002

作者简介: 刘彦权，男，博士，主治医师，讲师。研究方向：血液肿瘤与罕见病的科研、临床及高等医学教育研究。Email: doctorliuyanquan@163.com

通讯作者: 唐焕文，男，博士，教授，院长，博士生导师。Email: thw@gdmu.edu.cn

计量

出版历程

Abnormal expression and clinical significance of CXC chemokine receptor 1/2 in acute leukemia

Corresponding author: TANG Huanwen. Email: thw@gdmu.edu.cn

计量

出版历程

目录

作者简介:
刘彦权，男，博士，主治医师，讲师。研究方向：血液肿瘤与罕见病的科研、临床及高等医学教育研究。Email: doctorliuyanquan@163.com

通讯作者:
唐焕文，男，博士，教授，院长，博士生导师。Email: thw@gdmu.edu.cn