目的:探讨程序性死亡分子1配体-1(programmed death 1 ligand 1,PD-L1)表达水平在急性髓系白血病发生及转化过程、治疗中的临床意义。方法:(1)利用GEO软件和GEO2R计算方法,以P<0.05、|logFC|>1为条件,分析公共数据库常见免疫检查...目的:探讨程序性死亡分子1配体-1(programmed death 1 ligand 1,PD-L1)表达水平在急性髓系白血病发生及转化过程、治疗中的临床意义。方法:(1)利用GEO软件和GEO2R计算方法,以P<0.05、|logFC|>1为条件,分析公共数据库常见免疫检查点的表达情况;使用TCGA-LAML队列数据,利用Survival R包进行高表达PD-L1患者生存分析。(2)选取2017年10月至2023年3月在天津医科大学第二医院血液科确诊为急性髓系白血病的初治患者验证该结论,流式细胞术检测治疗前骨髓T细胞程序性死亡受体1(programmed cell death protein 1,PD-1)、CD34+原始细胞中PD-L1的表达水平,分析PD-1及PD-L1表达水平与患者临床特征、疗效及生存的相关性。结果:(1)急性髓系白血病(acute myeloid leukemia,AML)初诊患者中免疫检查点淋巴细胞活化基因3(lymphocyte lctivation gene 3,LAG3)、PD-1、PD-L1和T细胞免疫球蛋白黏蛋白分子3(T cell immunoglobulin domain and mucin domain-3,TIM3)表达较正常人高(P<0.05),初诊时PD-L1低表达组生存率高。(2)复发难治AML、继发性AML初诊时PD-L1表达水平更高,初诊AML患者PD-L1的高表达有复杂染色体核型、预后更差及生存更短的趋势。结论:PD-1/PD-L1信号通路可能参与髓系肿瘤细胞的免疫逃逸机制,其表达水平高与疾病恶性程度、进展呈正相关,与疗效和生存期呈负相关。展开更多
Background Recent studies have shown that interleukin-3 receptor α （CD123） is highly expressed on leukemia stem cells of patients with acute myeloid leukemia, and is correlated with tumor load and poor prognosis.Th...Background Recent studies have shown that interleukin-3 receptor α （CD123） is highly expressed on leukemia stem cells of patients with acute myeloid leukemia, and is correlated with tumor load and poor prognosis.The expression of CD123 may also be high in patients with myelodysplastic syndrome （MDS）.In this study, the expression and clinical significance of CD123 and granulocyte colony stimulating factor （G-CSF） receptor （CD114） on the bone marrow cells of patients with MDS were investigated to explore the molecular marker of the malignant clone of MDS.Methods Forty-two patients with MDS, who were diagnosed in the Hematological Department of General Hospital of Tianjin Medical University from 2008 to 2009, and twelve normal controls were enrolled in this study.Fluorescence activiated cell sorter （FACS） was used to measure the expression of CD123 on CD34＋CD38- cells and CD114 on CD34＋cells of the bone marrow of these patients and controls and the clinical significance was analyzed.The expression of CD114 on CD123＋CD34＋CD38- cells was further measured to explore the molecular marker of the malignant clone in MDS.Results MDS patients displayed significantly higher proportion of CD34＋CD38-/CD34＋ （（14.03±5.27）%） than normal controls （（7.70±4.36）%, P 〈0.05）.The expression rate of CD123＋CD34＋CD38-/CD34＋CD38- was significantly higher in MDS patients （（48.39±28.15）%） than that in normal controls （（8.75±11.71）%, P 〈0.01）.The expression level of CD123 was significantly correlated with the proportion of bone marrow blasts （r=0.457, P 〈0.05）.The expression rate of CD114＋CD34＋/CD34＋ was lower in MDS patients （（33.05±21.71）%） than that in normal controls （（38.99±19.07）%） but was not statistically significant （P 〉0.05）.The expression of CD114 on CD123＋CD34＋CD38- cells （（34.82±29.58）%） was significantly lower than that on CD123-CD34＋CD38- cells （（53.48±27.41）%） of M DS patients （P 〈0.05）.Conclusions MDS patients displayed higher proportion of CD34＋CD38-/CD34＋ than normal controls.CD123 was highly expressed in the bone marrow of the patients with MDS, significantly correlated with the proportion of bone marrow blasts, and thus might be the marker of MDS malignant clone.CD123＋CD34＋CD38- cells exhibited lower expression of G-CSF receptors, which might partly explain why MDS clone responds worse to G-CSF in vitro and in vivo.展开更多
文摘Background Recent studies have shown that interleukin-3 receptor α （CD123） is highly expressed on leukemia stem cells of patients with acute myeloid leukemia, and is correlated with tumor load and poor prognosis.The expression of CD123 may also be high in patients with myelodysplastic syndrome （MDS）.In this study, the expression and clinical significance of CD123 and granulocyte colony stimulating factor （G-CSF） receptor （CD114） on the bone marrow cells of patients with MDS were investigated to explore the molecular marker of the malignant clone of MDS.Methods Forty-two patients with MDS, who were diagnosed in the Hematological Department of General Hospital of Tianjin Medical University from 2008 to 2009, and twelve normal controls were enrolled in this study.Fluorescence activiated cell sorter （FACS） was used to measure the expression of CD123 on CD34＋CD38- cells and CD114 on CD34＋cells of the bone marrow of these patients and controls and the clinical significance was analyzed.The expression of CD114 on CD123＋CD34＋CD38- cells was further measured to explore the molecular marker of the malignant clone in MDS.Results MDS patients displayed significantly higher proportion of CD34＋CD38-/CD34＋ （（14.03±5.27）%） than normal controls （（7.70±4.36）%, P 〈0.05）.The expression rate of CD123＋CD34＋CD38-/CD34＋CD38- was significantly higher in MDS patients （（48.39±28.15）%） than that in normal controls （（8.75±11.71）%, P 〈0.01）.The expression level of CD123 was significantly correlated with the proportion of bone marrow blasts （r=0.457, P 〈0.05）.The expression rate of CD114＋CD34＋/CD34＋ was lower in MDS patients （（33.05±21.71）%） than that in normal controls （（38.99±19.07）%） but was not statistically significant （P 〉0.05）.The expression of CD114 on CD123＋CD34＋CD38- cells （（34.82±29.58）%） was significantly lower than that on CD123-CD34＋CD38- cells （（53.48±27.41）%） of M DS patients （P 〈0.05）.Conclusions MDS patients displayed higher proportion of CD34＋CD38-/CD34＋ than normal controls.CD123 was highly expressed in the bone marrow of the patients with MDS, significantly correlated with the proportion of bone marrow blasts, and thus might be the marker of MDS malignant clone.CD123＋CD34＋CD38- cells exhibited lower expression of G-CSF receptors, which might partly explain why MDS clone responds worse to G-CSF in vitro and in vivo.
