RhoH基因在初诊急性白血病患者中的表达差异及其临床意义
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摘要
目的:探讨RhoH基因在白血病患者骨髓细胞中的表达及其临床意义。方法:收集本院初诊白血病患者31例、非肿瘤患者15例。应用实时荧光定量PCR(real-time quantitative PCR,RQ-PCR)法检测骨髓细胞中RhoH表达,以RhoH的中位表达水平作为界值,将初诊患者分为RhoH高表达组和低表达组,并分析不同RhoH表达水平与患者初诊时临床特征和预后之间的关系。结果:31例AL患者骨髓细胞标本RhoH mRNA相对表达量显著低于对照组,ALL组显著低于AML组(P<0.05);与RhoH高表达组相比,RhoH低表达组骨髓原始细胞比例、LDH水平显著升高(P<0.05);而年龄、白细胞数、血红蛋白含量、血小板数、PCT、CRP值等临床特征无统计学差异(P>0.05)。在AML中,RhoH低表达组标准化疗后的复发率高于高表达组,而RhoH的表达与AML其他预后基因无相关性;在ALL中,RhoH低表达组标准化疗后的复发率与高表达组无统计学差异。结论:在急性白血病中RhoH可能参与疾病的发生。在AML中RhoH的表达与复发率呈负相关,可独立作为预后指标;在ALL中,RhoH可能通过其他作用机制参与疾病的过程。
Objective: To investigate the expression and clinical significance of RhoH gene in bone marrow cells of leukemia patients. Methods: 31 cases of leukemia and 15 cases of non-tumor as controls were collected. The expression of RhoH in bone marrow cells was detected by real-time quantitative PCR(RQ-PCR). The median expression level of RhoH was used as the cut-off value. The newly diagnosed patients were divided into RhoH high expression group and low expression group. The relationship of different RhoH expression levels with clinical features and prognosis of newly diagnosed patients was analyzed. Results: The mRNA expression of RhoH in the bone marrow cells of 31 cases of leukemia was significantly lower than that in the control group, mRNA expression of RhoH in the ALL group was significantly lower than that in AML group(P<0.05). Compared with the RhoH high expression group, the proportion of bone marraw blasts and LDH level in the RhoH low expression group was significantly increased(P<0.05), but there were no significant differences in clinical features such as age, white blood cell count, hemoglobin level, platelets count,PCT and CRP level(P>0.05). In AML, the recurrence rate after standard chemotherapy in RhoH low expression group was higher than that in high expression group, while the expression of RhoH not correlated with other prognostic genes of AML. In ALL, the recurrence rate in RhoH low expression group was not statistically significant different from that in high expression group. Conclusion: RhoH may be involved in the genesis of acute leukemia. In AML, RhoH expression negatively correlates with recurrence rate, which can be used as a prognostic indicator independently. In ALL, RhoH may participate in the disease process through other mechanism.
Objective: To investigate the expression and clinical significance of RhoH gene in bone marrow cells of leukemia patients. Methods: 31 cases of leukemia and 15 cases of non-tumor as controls were collected. The expression of RhoH in bone marrow cells was detected by real-time quantitative PCR(RQ-PCR). The median expression level of RhoH was used as the cut-off value. The newly diagnosed patients were divided into RhoH high expression group and low expression group. The relationship of different RhoH expression levels with clinical features and prognosis of newly diagnosed patients was analyzed. Results: The mRNA expression of RhoH in the bone marrow cells of 31 cases of leukemia was significantly lower than that in the control group, mRNA expression of RhoH in the ALL group was significantly lower than that in AML group(P<0.05). Compared with the RhoH high expression group, the proportion of bone marraw blasts and LDH level in the RhoH low expression group was significantly increased(P<0.05), but there were no significant differences in clinical features such as age, white blood cell count, hemoglobin level, platelets count,PCT and CRP level(P>0.05). In AML, the recurrence rate after standard chemotherapy in RhoH low expression group was higher than that in high expression group, while the expression of RhoH not correlated with other prognostic genes of AML. In ALL, the recurrence rate in RhoH low expression group was not statistically significant different from that in high expression group. Conclusion: RhoH may be involved in the genesis of acute leukemia. In AML, RhoH expression negatively correlates with recurrence rate, which can be used as a prognostic indicator independently. In ALL, RhoH may participate in the disease process through other mechanism.
引文
1 Vega FM,Ridley AJ.Rho GTPases in cancer cell biology.FEBSLett,2008;582(14):2093-2101.
2李凤茹,江华.Rho蛋白与恶性肿瘤相关性的研究进展.国际消化病杂志,2014;34(1):52-55.
3 Rath N,Olson MF.Rho-associated kinases in tumorigenesis:reconsidering ROCK inhibition for cancer therapy.Embo Rep,2012;13(10):900-908.
4 Wilson KF,Erickson JW,Antonyak MA,et al.Rho GTPases and their roles in cancer metabolism.Trends Mol Med,2013;19(2):74-82.
5 Deutsch AJ,Aigelsreiter A,Staber PB,et al.MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation.Blood,2007;109(8):3500-3504.
6 Liso A,Capello D,Marafioti T,et al.Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma.Blood,2006;108(3):1013-1020.
7 Li X,Bu X,Lu B,et al.The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function.Mol Cell Biol,2002;22(4):1158-1171.
8钟晓明,张伶.大鼠肉瘤蛋白Ras同源物之RhoH.生命的化学,2008;28(1):44-46.
9 Pruitt K,Der CJ.Ras and Rho regulation of the cell cycle and oncogenesis.Cancer Lett,2001;171(1):1-10.
10 Raftopoulou M,Hall A.Cell migration:Rho GTPases lead the way.Dev Biol,2004;265(1):23-32.
11 Reiniger L,B?d?r C,Bognár A,et al.Richter's and prolymphocytic transformation of chronic lymphocytic leukemia are associated with high mRNA expression of activation-induced cytidine deaminase and aberrant somatic hypermutation.Leukemia,2006;20(6):1089-1095.
12 Iwasaki T,Katsumi A,Kiyoi H,et al.Prognostic implication and biological roles of RhoH in acute myeloid leukaemia.Eur JHaematol,2010;81(6):454-460.
2李凤茹,江华.Rho蛋白与恶性肿瘤相关性的研究进展.国际消化病杂志,2014;34(1):52-55.
3 Rath N,Olson MF.Rho-associated kinases in tumorigenesis:reconsidering ROCK inhibition for cancer therapy.Embo Rep,2012;13(10):900-908.
4 Wilson KF,Erickson JW,Antonyak MA,et al.Rho GTPases and their roles in cancer metabolism.Trends Mol Med,2013;19(2):74-82.
5 Deutsch AJ,Aigelsreiter A,Staber PB,et al.MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation.Blood,2007;109(8):3500-3504.
6 Liso A,Capello D,Marafioti T,et al.Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma.Blood,2006;108(3):1013-1020.
7 Li X,Bu X,Lu B,et al.The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function.Mol Cell Biol,2002;22(4):1158-1171.
8钟晓明,张伶.大鼠肉瘤蛋白Ras同源物之RhoH.生命的化学,2008;28(1):44-46.
9 Pruitt K,Der CJ.Ras and Rho regulation of the cell cycle and oncogenesis.Cancer Lett,2001;171(1):1-10.
10 Raftopoulou M,Hall A.Cell migration:Rho GTPases lead the way.Dev Biol,2004;265(1):23-32.
11 Reiniger L,B?d?r C,Bognár A,et al.Richter's and prolymphocytic transformation of chronic lymphocytic leukemia are associated with high mRNA expression of activation-induced cytidine deaminase and aberrant somatic hypermutation.Leukemia,2006;20(6):1089-1095.
12 Iwasaki T,Katsumi A,Kiyoi H,et al.Prognostic implication and biological roles of RhoH in acute myeloid leukaemia.Eur JHaematol,2010;81(6):454-460.