| Objectives: Nur77(NR4A1) and Nor-1(NR4A3) are highly homologous orphan nuclear receptors, that regulate the transcription of overlapping target genes. The transcriptional activity of both proteins is regulated in a ligand-independent manner by cell- and stimulus-specific gene induction and protein phosphorylation. Nor-1 and Nur77 have been implicated in a variety of cellular processes, including the transduction of hormonal, inflammatory, mitogenic, apoptotic and differentiative signals. Cellular responses to these proteins suggest that they may function as homeostatic regulators of proliferation, apoptosis and differentiation, and thus may regulate cellular susceptibility to tumorigenesis. A research described a previously unsuspected function of Nor-1 and Nur77—as critical tumor suppressors of myeloid leukemogenesis. The abrogation of these proteins in mice led to rapidly lethal acute myeloid leukemia (AML), involving abnormal expansion of hematopoietic stem cells (HSCs) and myeloid progenitors, decreased expression of the AP-1 transcription factors JunB and c-Jun and defective extrinsic apoptotic (Fas-L and TRAIL) signaling. It is found that downregulation of NR4A3 (Nor-1) and NR4A1 (Nur77) was a common feature in leukemic blasts from human AML patients, irrespective of karyotype. Thus Nor-1 and Nur77 may provide potential targets for therapeutic intervention in AML.According to this,This research is aim at the expression of NR4A1 (Nur77) and NR4A3 (Nor1) gene in acute leukemia and normal control groups meanwhile analyze their clinical significance.Methods: The study enrolled 72 acute leukemia (AL) patients including 48 newly diognosed acute myelociod leukemia cases(AML),8 complete remission ones (CR) and 16 newly diognosed acute lymphocytic leukemia(ALL) cases. 20 volunteers served as normal contrals (NC). The expression level of NR4A1 (Nur77) and NR4A3 (Nor1) mRNA was measured by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and fluorescent quantitative RT-PCR.Results:Analysis the expression of NR4A1 (Nur77) and NR4A3 (Nor1) mRNA in AL,CR and NC group by RT-PCR and FQ- RT-PCR.1 We measured the ratio of the positive expression of Nur77 by RT-PCR: The ratio of the positive expression of Nur77(50%) in newly diagnosed AML patients were significantly lower than in NC group (90%),(X2=9.5648,P=0.002<0.05).The positive rate in newly diagnosed ALL patients is 87.5%(14/16),Compared with normal controls (positive rate is 90%) , There is no statistical significance (P=1.000>0.05).2 Using FQ-RT-PCR methods, we measured the expression of Nur77 in each group: The expression of Nur77 in newly diagnosed AML patients is significantly lower than in normal controls (NC) (P=0.001<0.05). The expression of Nur77 in CR patients is lower than in normal controls too, it also has statistical significance.(P=0.002<0.05).The expression level of Nur77 in CR group is higher than that in newly diagnosed AML group.But there was no statistical significance (P=0.452>0.05). The expression of Nur77 in newly diagnosed ALL patients and AML patients have significant difference (P=0.0010<0.05). Compared between newly diagnosed ALL group and NC group, there is no statistical significance. (P=0.11>0.05).3 We measured the ratio of the positive expression of Nor1 by RT-PCR: The ratio of the positive expression of Nor1(25%) in newly diagnosed AML group is significantly lower than that in NC group (90%), (X2=24.1937 ,P=0.0001<0.05)。The positive rate in newly diagnosed ALL patiens is 75%, Compared with normal controls (positive rate is 90%), There is no statistical significance (P=1.000>0.05).4 We measured the expression of Nor1 in each group using FQ-RT-PCR: The expression level of Nor1 in newly diagnosed AML group is significantly lower than in normal controls (NC) (P=0.032<0.05).Compared between CR group and NC group, the expression level of Nor1 in CR group is lower than that in NC group, but it has no significant difference.(P=0.116>0.05). In newly diagnosed AML patients it's lower than in CR group and it has statistical significance(P=0.001<0.05).The expression level of Nor1 in newly diagnosed ALL patients is higher than in newly diagnosed AML group and it has significant difference (P=0.02<0.05). But compared with NC group, there is no statistical significance (P=0.058>0.05).5 In the 48 cases of newly diagnosed AML patients, 24 of whom showed Nur77 positive ,and the CR rate of Nur77 positive group is 70.8%(17/24),which is higher than that of Nur77 negative group (33.3%(8/24)), The difference is statistical significance (X2=6.762,P=0.009<0.05). In the 12 Nor1 positive patients,the CR rate(83.3%,10/12) is significantly higher than that of Nor1 negative group(41.7%,15/36), It has statistical significance (X2=6.261,P=0.012<0.05)6 The expression level of Nur77 in newly diagnosed AML group is negative correlated with the peripheral blood leucocyte (PBL), (r=-0.598)and that of Nor1 is the same(r=-0.498). They all have statistical significance (P<0.05).7 The expression level of Nur77 and Nor1 in different FAB sub-type AML patients have no statistical significance (P>0.05).Conclusion:1 In newly diagnosed acute myeloid leukemia patients,the expression level of Nur77 mRNA and Nor1 mRNA is significantly lower than that in NC group(P<0.05), In newly diagnosed acute lymphoblastic leukemia patients, the expression level of Nur77 mRNA and Nor1 mRNA have no difference(P>0.05). It suggests that Nur77 and Nor1 are associated with leukemia subtype.2 In newly diagnosed AML patients, the CR rate in Nur77 positive group or Nor1 positive group is significantly higher than that in Nur77 negative group or Nor1 negative group, which indicates Nur77 and Nor1 may have close relationship with the prognosis of leukemia patients.3 The expression level of Nur77 and Nor1 in newly diagnosed AML patients have negative correlation with the peripheral blood leucocyte (PBL), it suggests that Nur77 and Nor1 may be associated with the outbreak and development of acute myeloid leukemia ,they also have relationship with the prognosis of leukemia patients4 The expression level of Nur77 and Nor1 in different FAB sub-type AML patients have no statistical significance.P>0.05. It shows that they have no relationship with the FAB sub-types in AML patients.
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