急性髓细胞性白血病患者骨髓淋巴细胞亚群分析及其临床意义

doi:10.16150/j.1671-2870.2020.04.016

摘要/Abstract

摘要：

目的： 分析急性髓细胞性白血病（acute myeloid leukemia,AML）患者的骨髓淋巴细胞亚群分布,比较不同疾病阶段、不同预后风险患者间的骨髓免疫功能差异,并探讨其临床意义。方法： 选取131例AML确诊患者治疗前的骨髓样本,采用多色流式细胞术分析样本中各淋巴细胞亚群（CD4⁺、CD8⁺、CD19⁺等）占总淋巴细胞的百分比及CD4⁺/CD8⁺比值,并将结果与公共数据平台获取的健康者骨髓样本淋巴细胞亚群结果进行比较。AML患者分别为初诊（94例）、继发（18例）及化疗缓解后复发患者（19例）,共3组,比较各组间淋巴细胞亚群差异;进一步根据细胞遗传学异常将初诊AML分为低危、中危及高危组,比较3组间的淋巴细胞亚群差异。回溯复发组患者初发时的骨髓样本检测结果,配对比较初发与复发时样本中淋巴细胞亚群的变化。结果： 与健康者比较,AML患者骨髓样本中CD8⁺ T淋巴细胞百分比显著增高[（31.73%±12.38)%比(21.40%±7.33%),P<0.001],CD19⁺ B淋巴细胞百分比及CD4⁺/CD8⁺比值显著降低（9.62%比14.03%,P<0.01;1.04比1.48,P<0.05）;复发患者骨髓样本中的CD8⁺ T淋巴细胞百分比较初诊患者显著增高[（41.56±11.64%）比（29.86±12.20%）,P<0.001],CD19⁺ B淋巴细胞百分比及CD4⁺/CD8⁺比值显著降低（4.18%比11.82%,P<0.05;0.59比1.12,P<0.05）。配对比较显示,复发患者的CD19⁺ B细胞百分比与其初发时比较显著降低（2.40%比12.41%,P<0.05）。94例初诊AML不同预后风险度的3组间各淋巴细胞亚群比较,差异无统计学意义。各组间自然杀伤（natural killer, NK）细胞百分比差异无统计学意义。结论： AML患者骨髓呈明显的体液免疫及细胞免疫功能抑制状态,AML复发患者的骨髓免疫功能抑制较其初发时更为显著,提示检测AML患者骨髓淋巴亚群的分布情况可能是评估疾病预后的有效指标,对临床使用免疫调节药物治疗具有一定的指导意义。

关键词: 急性髓细胞性白血病, 淋巴细胞亚群, 复发, B淋巴细胞, T淋巴细胞

Abstract:

Objective: To investigate the distribution of bone marrow lymphocyte subsets in patients with acute myeloid leukemia (AML),and comparing the bone marrow immune function between patients at different stage of disease and with different prognostic risk, and exploring their related clinical significance. Methods: The bone marrow samples from 131 patients with AML before treatment were collected, and the lymphocyte subsets CD4⁺ T cells, CD8⁺ T cells and CD19⁺ B cells were identified by multi-color flow cytometry for determining the percentages of lymphocyte subsets and CD4⁺/CD8⁺ ratio. The results were compared with that of healthy bone marrow samples obtained from the public data platforms. The AML patients included de novo cases (94 cases), secondary cases （18 cases）, and relapsing cases after chemotherapy （19 cases）. The de novo AML were categorized into low risk, intermediate risk and high risk groups according to the cytogenetic abnormality. Differences in lymphocyte subsets between the three groups and between the three different risk levels were compared. In relapsing patients, the percentages of lymphocyte subsets at onset were compared with that at relapse. Results: Compared with healthy subjects, AML patients had a higher percentage of CD8⁺ T cells (31.73%±12.38% vs 21.40±7.33%, P<0.001) and lower percentage of CD19⁺ B cells ( 9.62% vs 14.03%, P<0.01) and lower ratio of CD4⁺/CD8⁺ (1.04 vs 1.48, P<0.05). When compared with de novo patients, relapsing patients had higher CD8⁺ T cells (41.56%±11.64% vs 29.86%±12.20%, P<0.001), but lower CD19⁺ B cells ( 4.18% vs 11.82%, P<0.05) and CD4⁺/CD8⁺ ratio (0.59 vs 1.12, P<0.05). Paired comparison showed that relapsing patients had significant lower percentage of CD19⁺ B cells than that at onset(2.40% vs 12.41%, P<0.05). There were no significant differences in distribution of lymphocyte subsets between different risk level groups of de novo AML. The percentages of NK cells between the three groups were not different significantly. Conclusions: The bone marrow of AML patients showes obvious suppression of humoral immunity and cellular immunity. The suppression of bone marrow immune function is obviously more severe in patients with relapsing AML than in de novo. It is suggested that the distribution of bone marrow lymphatic subsets may be an effective indicator for detecting and assessing the prognosis of the disease.

Key words: Acute myeloid leukemia, Lymphocyte subsets, Relapse, B lymphocyte, T lymphocyte

中图分类号:

R733.7

高燕婷, 赵金艳, 王娟, 李佳, 许雯, 李莉, 蔺丽慧. 急性髓细胞性白血病患者骨髓淋巴细胞亚群分析及其临床意义[J]. 诊断学理论与实践, 2020, 19(04): 407-413.

GAO Yanting, ZHAO Jinyan, WANG Juan, LI Jia, XU Wen, LI Li, LIN Lihui. Analysis of bone marrow lymphocyte subsets in patients with acute myeloid leukemia and its clinical significance[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(04): 407-413.

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分组	初诊AML			继发AML（n=18）	复发AML（n=19）
分组	低危组（n=36）	中危组（n=27）	高危组（n=31）	继发AML（n=18）	复发AML（n=19）
性别(女/男)	14/22	11/16	12/19	8/10	4/15
中位年龄(岁）	53(18~77)	38(26~68)	54(25~72)	53(33~78)	48(17~70)
融合基因
RUNX1-RUNX1T1	6(16.67%)				1(5.26%)
KMT2A重排			2(6.45%)		3(15.79%)
CBFB-MYH11	7(19.44%)				3(15.79%)
突变基因
NPM1	14(38.89%)	1(3.70%)	2(6.45%)		1(5.26%)
NPM1突变伴低水平FLT3-ITD	2(5.56%)		1(3.23%)
NPM突变伴高水平FLT3-ITD		1(3.70%)	1(3.23%)
野生型NPM1伴低水平FLT3-ITD		4(14.81%)	4(12.90%)		2(10.53%)
野生型NPM1伴高水平FLT3-ITD			1(3.23%)
CEBPA双突变	9(25.00%)
RUNX1	2(5.56%)		7(22.58%)	1(5.56%)	2(10.53%)
ASXL1	9(25.00%)		21(67.74%)	10(55.56%)	2(10.53%)
TP53			5(16.13%)	5(27.78%)	2(10.53%)