慢性粒细胞白血病骨髓巨噬细胞表达与细胞因子的相关性

目的 探讨慢性粒细胞白血病(CML)患者骨髓中巨噬细胞及白细胞介素(IL)-1β、IL-2、IL-4、IL-10、γ干扰素(INF-γ)的表达及相关性以明确其临床意义.方法 选择CML慢性期30例(CML-CP组)、加速期21例(CML-AP组)、急变期20例(CML-BP组)、经治疗后完全缓解的患者44例、未缓解7例以及30例缺铁性贫血患者(对照组),采用免疫组化染色法检测上述各组患者骨髓组织中CD68、CD163的表达变化;应用流式细胞仪分析相应患者骨髓IL-1β、IL-2、IL-4、IL-10、INF-γ表达;比较骨髓巨噬细胞在CML患者不同时期骨髓组织CD68、CD163的表达差异与IL-1β、IL-2、IL-4、IL-10、INF-γ表达变化的关系.结果 CML各组患者骨髓组织中CD68、CD163均有不同程度的表达,且随着病情的进展表达逐渐增高,即对照组＜CML-CP组＜CML-AP组＜CML-BP组,组间比较差异有统计学意义(P＜0.05);同时,CD163与CD68阳性细胞数密切相关(P＜0.05).与对照组比较,CML-CP组骨髓IL-2、INF-γ明显降低(P＜0.05),IL-1β、IL-4、IL-10表达明显升高(P＜0.05);随着病情进展,IL-2、INF-γ表达逐渐降低,即对照组＞CML-CP组＞CML-AP组＞CML-BP组,其组间差异有统计学意义(P＜0.05),且与CD163表达呈负相关;IL-1β、IL-4、IL-10表达逐渐升高,对照组＜CML-CP组＜CML-AP组＜CML-BP组,组间差异有统计学意义(P＜0.05),并与CD163表达呈正相关.患者经治疗完全缓解后,CD68及CD163仍高于对照组(P＜0.05);IL-2、INF-γ有所回升,但仍低于对照组(P＜0.05),IL-1β、IL-4、IL-10有所降低,同样也高于对照组(P＜0.05).未缓解组所测指标与CML-BP组相比,差异无统计学意义(P＞0.05).结论 巨噬细胞在CML患者骨髓中的异常浸润并逐渐从M1型向M2型巨噬细胞激化及IL-1β、IL-2、IL-4、IL-10、INF-γ的异常表达,改变了正常骨髓微环境,有利于白血病细胞的生存和增殖分化,可能与CML的发生、发展相关.

Correlation study between the expression of macrophages and cytokines in bone marrow of CML patients

Objective To detect the expression of macrophages and the interleukin IL)-1β,IL-2,IL-4,IL-10 and tissue necrosis factor (INF)-γ in bone marrow of chronic myeloid leukemia (CML) patients,and to analyze their correlations and clinical significances.Methods The experimental group included 147 patients,among whom there were 30 cases of CML in chronic phase (CML-CP),21 cases of CML in accelerated phase (CML-AP),20 cases of CML in blastic phase (CML-BP),44 cases of complete remission after treatment,and 7 cases without remission.And 30 cases of iron deficiency anemia were included as control group.Immunohistochemical technique was used to detect the expression levels of CD68 and CD163,and flow cytometry was used to detect the expression levels of IL-1β,IL-2,IL-4,IL-10 and INF-γin bone marrow.Results CD163 and CD68 were expressed in different degrees in bone marrow of CML patients,and gradually increased as the progression of the disease,as significantly highest in CML-BP group,and followed by CMP-AP,CML-CP,and control groups (P ＜ 0.05).The CD68 positive cell count was closely correlated to CD163 positive cell count (P ＜ 0.05).Compared with the control group,the expression levels of IL-2 and INF-γ were significantly reduced as the progress of the disease,and negatively correlated with the expression of CD163;as the expression levels of IL-2 and INF-γ were significantly highest in control group,and followed by CML-CP,CML-AP and CML-BP (P ＜ 0.05).The expression levels of IL-1 β,IL-4 and IL-10 were significantly increased,and positively correlated with the expression of CD163;as the expression levels of IL-1 β,IL-4 and IL-10 were significantly lowest in control group,and followed by CML-CP,CML-AP and CML-BP groups (P ＜ 0.05).In patients with complete remission after treatment,the expression levels of CD68 and CD163 were still higher than those in control group (P ＜ 0.05);with significantly lower IL-2 and INF-γ (P ＜ 0.05).There was no statistical significance when compared the results between non-remission group and CML-BP group (P ＞ 0.05).Conclusion Abnormal infiltration of macrophages in the bone marrow is observed in CML patients.The nacrophage activation from Type M1 to Type M2;abnormal expression of IL-1 β,IL-2,IL-4,IL-10 and INF-γ;and microenvironment of bone marrow changes may be related to the occurrence and development of CML.