RYBP、BMI1及LSD1蛋白在急性白血病中表达情况的研究
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摘要
目的:
观察PcG蛋白RYBP(Ring1 and YY1-binding protein,RYBP)、BMI1(B-cell specific moloney leukemia virusinsertion site 1)蛋白及组蛋白去甲基化酶LSD1(Lysine specific demethylase 1)在急性白血病中的表达状况,初步探索它们在急性白血病中表达的临床意义。
方法:
应用蛋白质免疫印迹(western blot)技术,分别检测急性单核细胞白血病细胞株SHI-1、急性早幼粒细胞白血病细胞株HL-60、慢性粒细胞白血病细胞株K562及初治急性白血病(AL)、急性白血病化疗后达完全缓解(ALCR)患者和对照(非恶性血液病)患者的骨髓单个核细胞(BM-MNCs)中RYBP、BMI1及LSD1蛋白的表达情况,初步分析它们在急性白血病中的表达规律及临床意义。
结果:
1. RYBP表达情况:SHI-1、HL-60及K562细胞株RYBP表达均为强阳性;21例非恶性血液病对照中RYBP表达阴性。AL组的RYBP表达阳性率为72.5%,ALCR组阳性率为13%,AL组的RYBP表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05);其中初治的急性髓系白血病(AML)组和急性淋巴细胞白血病(ALL)组RYBP表达阳性率及表达量均明显高于对照组(P<0.05),而AML和ALL两组间的RYBP表达阳性率及表达量无显著差异(P>0.05)。
2. BMI1表达情况:SHI-1、HL-60及K562细胞株BMI1蛋白表达均为强阳性;8例非恶性血液病对照及24例ALCR组中BMI1蛋白表达阴性。AL组的BMI1蛋白表达阳性率为61.0%。AL组的BMI1蛋白表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05);其中初治的急性髓系白血病(AML)组和急性淋巴细胞白血病(ALL)组BMI1蛋白表达阳性率及表达量均明显高于对照组(P<0.05),而AML和ALL两组间的BMI1蛋白表达阳性率及表达量无显著差异(P>0.05)。
3.研究RYBP及BMI1在AL中的相关性发现:在AML中RYBP与BMI1蛋白均高表达,表达阳性率及表达量无显著差异(P>0.05);RYBP与BMI1两者表达水平有显著相关性(r=0.640, P<0.01)。
4. LSD1表达情况:SHI-1、HL-60及K562细胞株LSD1蛋白表达均为强阳性;17例非恶性血液病对照中LSD1蛋白表达阴性。AL组的LSD1蛋白表达阳性率为78.6%,ALCR组阳性率为4.2%,AL组的LSD1蛋白表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05);其中初治的急性髓系白血病(AML)组和急性淋巴细胞白血病(ALL)组LSD1蛋白表达阳性率及表达量均明显高于对照组(P<0.05),而AML和ALL两组间的LSD1蛋白表达阳性率及表达量无显著差异(P>0.05)。
结论:
1.血液系统非恶性疾病患者骨髓MNCs低表达RYBP、BMI1及LSD1蛋白,而白血病细胞株细胞明显地高表达;在急性白血病患者,初诊时骨髓MNCs中RYBP、BMI1及LSD1蛋白表达量大多明显升高,治疗后达到完全缓解时表达量明显下降。这些初步结果说明白血病细胞高表达RYBP、BMI1及LSD1蛋白。提示RYBP、BMI1及LSD1蛋白与急性白血病密切相关,可能在急性白血病的发病中起作用并有可能开发成为急性白血病新的生物标志物。
2. RYBP与BMI1的表达水平在AML中显著相关,提示在急性髓细胞白血病发病中可能存在RYBP与BMI1相互作用。提示在白血病发病过程中PcG蛋白可能形成相互作用异常多蛋白复合体。
Objective:
To investigate the expression and its significance of RYBP ( Ring1 and YY1-binding protein)、BMI1(B-cell specific moloney leukemia virusinsertion site 1)protein and LSD1(Lysine specific demethylase 1)in acute leukemia (AL).
Methods:
RYBP、BMI1and LSD1 protein level was assessed by western blot in the bone marrow mononuclear cells (BM-MNCs) of acute leukemia patients, complete remission (ALCR) patients and controls(patients without malignant hematological diseases), as well as leukemia cell line SHI-1、HL-60 and K562.The pattern of RYBP、BMI1 and LSD1 protein expression and the significance of RYBP、BMI1 and LSD1 protein expression level in leukemia patients were explored.
Results:
1. The expression of RYBP was positive in leukemia cell line SHI-1、HL-60 and K562 but negative in 21 controls. The RYBP was expressed in 72.5% AL patients and 13% ALCR patients. The expression rate and level of RYBP in AL was significantly higher than that in ALCR and controls (P<0.05). The expression of RYBP in AML and ALL patients was significantly higher than that in controls(P<0.05), while the expression rate and level of RYBP between AML and ALL had no statistical difference (P>0.05).
2. The expression of BMI1 protein was positive in leukemia cell line SHI-1、HL-60 and K562 but negative in 8 controls as well as 24 ALCR patients. The BMI1 was expressed in 61.0% AL patients.The expression rate and level of BMI1 in AL was significantly higher than that in ALCR and controls (P<0.05). The expression of BMI1 protein in AML and ALL patients was significantly higher than that in controls(P<0.05), while the expression rate and level of BMI1 protein between AML and ALL had no statistical difference (P>0.05).
3. In AML,both RYBP and BMI1 were highly expressed.The expression rate and level between RYBP and BMI1 had no significant difference and the expression of RYBP was positively correlated with that of BMI1 in AML(r=0.640,P<0.01).
4. The expression of LSD1 protein was positive in leukemia cell line SHI-1、HL-60 and K562 but negative in 17 controls. The LSD1 was expressed in 78.6% AL patients and 4.2% ALCR patients. The expression rate and level of LSD1 protein in AL was significantly higher than that in ALCR and controls (P<0.05). The expression of LSD1 protein in AML and ALL patients was significantly higher than that in controls(P<0.05), while the expression rate and level of LSD1 protein between AML and ALL had no statistical difference (P>0.05).
Conclusion:
1. The expression of RYBP、BMI1 and LSD1 protein were low in patients without malignant hematological diseases,while that in leukemia cell line were significantly high.The expression level of RYBP、BMI1 and LSD1 protein high in newly diagnosed leukemia changed to low after complete remission.It is concluded that RYBP、BMI1 and LSD1 protein were over-expressed significantly in acute leukemia, suggesting that RYBP、BMI1 and LSD1 protein are associate with acute leukemia.They may be involved in the occurrence process of acute leukemia, thus they may be developed as biomarkers for acute leukemia.
2. The expression of RYBP was positively correlated with that of BMI1 in AML. suggestting that in the pathogenesis of AML,RYBP may interact with BMI1 and PcG proteins may form unusually large protein complexes in the occureence process of acute leukemia.
观察PcG蛋白RYBP(Ring1 and YY1-binding protein,RYBP)、BMI1(B-cell specific moloney leukemia virusinsertion site 1)蛋白及组蛋白去甲基化酶LSD1(Lysine specific demethylase 1)在急性白血病中的表达状况,初步探索它们在急性白血病中表达的临床意义。
方法:
应用蛋白质免疫印迹(western blot)技术,分别检测急性单核细胞白血病细胞株SHI-1、急性早幼粒细胞白血病细胞株HL-60、慢性粒细胞白血病细胞株K562及初治急性白血病(AL)、急性白血病化疗后达完全缓解(ALCR)患者和对照(非恶性血液病)患者的骨髓单个核细胞(BM-MNCs)中RYBP、BMI1及LSD1蛋白的表达情况,初步分析它们在急性白血病中的表达规律及临床意义。
结果:
1. RYBP表达情况:SHI-1、HL-60及K562细胞株RYBP表达均为强阳性;21例非恶性血液病对照中RYBP表达阴性。AL组的RYBP表达阳性率为72.5%,ALCR组阳性率为13%,AL组的RYBP表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05);其中初治的急性髓系白血病(AML)组和急性淋巴细胞白血病(ALL)组RYBP表达阳性率及表达量均明显高于对照组(P<0.05),而AML和ALL两组间的RYBP表达阳性率及表达量无显著差异(P>0.05)。
2. BMI1表达情况:SHI-1、HL-60及K562细胞株BMI1蛋白表达均为强阳性;8例非恶性血液病对照及24例ALCR组中BMI1蛋白表达阴性。AL组的BMI1蛋白表达阳性率为61.0%。AL组的BMI1蛋白表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05);其中初治的急性髓系白血病(AML)组和急性淋巴细胞白血病(ALL)组BMI1蛋白表达阳性率及表达量均明显高于对照组(P<0.05),而AML和ALL两组间的BMI1蛋白表达阳性率及表达量无显著差异(P>0.05)。
3.研究RYBP及BMI1在AL中的相关性发现:在AML中RYBP与BMI1蛋白均高表达,表达阳性率及表达量无显著差异(P>0.05);RYBP与BMI1两者表达水平有显著相关性(r=0.640, P<0.01)。
4. LSD1表达情况:SHI-1、HL-60及K562细胞株LSD1蛋白表达均为强阳性;17例非恶性血液病对照中LSD1蛋白表达阴性。AL组的LSD1蛋白表达阳性率为78.6%,ALCR组阳性率为4.2%,AL组的LSD1蛋白表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05);其中初治的急性髓系白血病(AML)组和急性淋巴细胞白血病(ALL)组LSD1蛋白表达阳性率及表达量均明显高于对照组(P<0.05),而AML和ALL两组间的LSD1蛋白表达阳性率及表达量无显著差异(P>0.05)。
结论:
1.血液系统非恶性疾病患者骨髓MNCs低表达RYBP、BMI1及LSD1蛋白,而白血病细胞株细胞明显地高表达;在急性白血病患者,初诊时骨髓MNCs中RYBP、BMI1及LSD1蛋白表达量大多明显升高,治疗后达到完全缓解时表达量明显下降。这些初步结果说明白血病细胞高表达RYBP、BMI1及LSD1蛋白。提示RYBP、BMI1及LSD1蛋白与急性白血病密切相关,可能在急性白血病的发病中起作用并有可能开发成为急性白血病新的生物标志物。
2. RYBP与BMI1的表达水平在AML中显著相关,提示在急性髓细胞白血病发病中可能存在RYBP与BMI1相互作用。提示在白血病发病过程中PcG蛋白可能形成相互作用异常多蛋白复合体。
Objective:
To investigate the expression and its significance of RYBP ( Ring1 and YY1-binding protein)、BMI1(B-cell specific moloney leukemia virusinsertion site 1)protein and LSD1(Lysine specific demethylase 1)in acute leukemia (AL).
Methods:
RYBP、BMI1and LSD1 protein level was assessed by western blot in the bone marrow mononuclear cells (BM-MNCs) of acute leukemia patients, complete remission (ALCR) patients and controls(patients without malignant hematological diseases), as well as leukemia cell line SHI-1、HL-60 and K562.The pattern of RYBP、BMI1 and LSD1 protein expression and the significance of RYBP、BMI1 and LSD1 protein expression level in leukemia patients were explored.
Results:
1. The expression of RYBP was positive in leukemia cell line SHI-1、HL-60 and K562 but negative in 21 controls. The RYBP was expressed in 72.5% AL patients and 13% ALCR patients. The expression rate and level of RYBP in AL was significantly higher than that in ALCR and controls (P<0.05). The expression of RYBP in AML and ALL patients was significantly higher than that in controls(P<0.05), while the expression rate and level of RYBP between AML and ALL had no statistical difference (P>0.05).
2. The expression of BMI1 protein was positive in leukemia cell line SHI-1、HL-60 and K562 but negative in 8 controls as well as 24 ALCR patients. The BMI1 was expressed in 61.0% AL patients.The expression rate and level of BMI1 in AL was significantly higher than that in ALCR and controls (P<0.05). The expression of BMI1 protein in AML and ALL patients was significantly higher than that in controls(P<0.05), while the expression rate and level of BMI1 protein between AML and ALL had no statistical difference (P>0.05).
3. In AML,both RYBP and BMI1 were highly expressed.The expression rate and level between RYBP and BMI1 had no significant difference and the expression of RYBP was positively correlated with that of BMI1 in AML(r=0.640,P<0.01).
4. The expression of LSD1 protein was positive in leukemia cell line SHI-1、HL-60 and K562 but negative in 17 controls. The LSD1 was expressed in 78.6% AL patients and 4.2% ALCR patients. The expression rate and level of LSD1 protein in AL was significantly higher than that in ALCR and controls (P<0.05). The expression of LSD1 protein in AML and ALL patients was significantly higher than that in controls(P<0.05), while the expression rate and level of LSD1 protein between AML and ALL had no statistical difference (P>0.05).
Conclusion:
1. The expression of RYBP、BMI1 and LSD1 protein were low in patients without malignant hematological diseases,while that in leukemia cell line were significantly high.The expression level of RYBP、BMI1 and LSD1 protein high in newly diagnosed leukemia changed to low after complete remission.It is concluded that RYBP、BMI1 and LSD1 protein were over-expressed significantly in acute leukemia, suggesting that RYBP、BMI1 and LSD1 protein are associate with acute leukemia.They may be involved in the occurrence process of acute leukemia, thus they may be developed as biomarkers for acute leukemia.
2. The expression of RYBP was positively correlated with that of BMI1 in AML. suggestting that in the pathogenesis of AML,RYBP may interact with BMI1 and PcG proteins may form unusually large protein complexes in the occureence process of acute leukemia.
引文
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