【摘要】 目的:探讨慢性粒细胞白血病(CML)患者骨髓M2型巨噬细胞与白血病干细胞(leukemic stem cells,LSC)的相关性,并明确其意义。方法:采用免疫组织化学染色法检测CML慢性期(CML~-CP)30例、加速期(CML~-AP)21例、急变期(CML~-BP)15例、经治疗后缓解患者44例(缓解组)、未缓解患者7例(未缓解组)及30例缺铁性贫血患者(对照组)骨髓组织中CD163~+的表达变化,比较M2型巨噬细胞在CML患者不同时期骨髓组织中的表达差异;用流式细胞仪检测相应CML各期CD34~+CD38~-CD123~+LSC的表达,并与正常对照组进行比较。结果:CML各组患者骨髓中CD163~+巨噬细胞有不同程度的表达,与对照组相比明显增高(P<0.05)。随着病情的进展,CD163~+巨噬细胞的浸润密度逐渐增高,CMLBP高于CML~-AP(P<0.05),CML~-AP高于CML~-CP(P<0.05),缓解组CD163~+均有所降低,但仍高于对照组(P<0.05),未缓解组与CML~-BP相比有增高趋势,但差异无统计学意义(P>0.05)。在CML~-CP患者中,CD34~+CD38~-CD123~+细胞明显高于对照组(P<0.05),随着病情进展,表达逐渐增高,即CML~-BP>CML~-AP>CML~-CP,且组间差异有统计学意义(P<0.05);患者经治疗完全缓解后,CD34~+CD38~-CD123~+细胞表达有所降低,但仍高于对照组(P<0.05);未缓解组CD34~+CD38~-CD123~+细胞有增高趋势,但与CML~-BP相比无统计学意义(P>0.05);经相关性分析,CD163~+巨噬细胞浸润密度与LSC阳性细胞数呈明显正相关(P<0.05)。结论:M2巨噬细胞在CML患者骨髓中具有较高的浸润密度,且在CML不同时期浸润密度不同;CD34~+CD38~-CD123~+细胞在不同时期的CML中均有不同程度表达。M2型巨噬细胞与LSC可能通过直接或间接作用,参与CML的发生、发展及预后。有望为CML的发生、发展机制、治疗及预后判断提供新的思路和理论依据。更多还原

【Abstract】 Objective:To discuss the correlation between bone marrow M2 macrophages in chronic myelogenous leukemia(CML) patients and leukemic stem cells(leukemic stem cells,LSC) and to clarify bone marrow macrophages’ role in CML patients.Method:The expression of CD163~+ in bone marrow was detected by immunohistochemical staining in chronic phase(CML~-CP) 30 cases,accelerated phase(CML~-AP) 21 cases,blastic phase(CML~-BP) 15 cases,remission patients 44 cases after treatment,no remission patients with 7 cases and 30 cases of iron deficiency anemia patients.Flow cytometry was used to detect CD34~+CD38~-CD123~+ LSC.Result:There were different expression levels of CD163~+ in CML patient bone marrow.Compared with normal control,the expressions in CML patients were significantly high.With the patient progress,CD163~+ infiltration density gradually increased.The infiltration density in CML~-BP group was higher than that in CML~-AP group(P<0.05),the density in CML~-AP group was higher than that in CML~-CP group(P<0.05),the density in remission patients was low,and was still higher compared with normal control(P<0.05).There was increase trend in without remission group compared with CML~-BP group(P>0.05).The number of CD34~+CD38~-CD123~+ positive cells in CML~-CP patients was significantly higher than in normal control(P<0.05).With the progress of the disease,the expression gradually increased,the CML~-BP> CML~-AP> CML~-CP,and there were statistical significance between groups(P<0.05).CD34~+CD38~-CD123~+ cells in completed remission group were decreased and were still higher than normal control(P<0.05).There was no statistical significance in without remission group compared to AP.After correlation analysis,CD163~+ macrophage infiltration density was positively correlated with LSC~-positive cells(P<0.05).Conclusion:Macrophages have higher infiltration density in CML different phases and gradually polarized to M2 macrophages.Infiltration density is different in different CML phages.CD34~+CD38~-CD123~+ are different expression levels in CML different phases.M2 macrophages closely relate to CML occurrence,development and prognosis.It can supply new ideas and theoretical basis for CML treatment and prognosis judgment.更多还原