| Objectives:Cyclin is a kind of cell cycle regulatory factor, It's expression is changeing in every cell cycle stage switching. At different stage, different cyclins bind or separate with coordinate cyclin-dependent-kinase (CDKs), resulting in it substrate phosphorylation and dephosphorylation. It regulate cell cycle. Cyclin H is diffferent from other cyclins,cyclin H is existing in whole cell cycle and is not flucture. cyclin H is a new cyclin, can enhance CDK7 phosphorylation and activate other CDKs. Thus, people presume CDK7/cyclin H may be upstream element in CDK/cyclins cascade reaction proceeding. CDK7/cyclin H is high expressed in some tumors, and its high expression associates with poor prognosis. The expression and significance of CDK7/cyclin H in leukemia remains to be elucidated. This study intended to investigate the expression and clinical significance of cyclin H and CDK7 in acute leukemia.Methods: The expression of cyclin H,CDK7 mRNA and P53,cyclin E2,CDK2 mRNA were measured in 101 adult acute leukemia patients(including 69 de novo acute leukemia patients, 13 relapsed patients and 19 complete remission patients), and 15 samples of healthy controls(HC) by semi-quantity reverse transcription polymers chain reaction(RT-PCR). Results:1 Cyclin H mRNA is positive in two AL lines:HL60, K562. cyclin H mRNA was detected in some samples only. The positive rate and average expression level of cyclin H mRNA in de novo AL patients was( 66.7%, 0.9100±0.6559); The positive rate and average expression level of cyclin H mRNA in relapsed patients was (76.9%, 0.9600±0.5045); The positive rate and average expression level of cyclin H mRNA in remission patients was (36.8%, 0.5505±0.2663); The positive rate and average expression level of cyclin H mRNA in healthy controls was (20%, 0.3420±0.2352); Cyclin H mRNA positive rates and expression levers in de novo AL patients and relapsed patients was higher than that of complete remission patients and healthy controls, (P<0.05). The positive rate and average expression lever of cyclin H mRNA in relapsed patients was higher than that of de novo AL patients and in complete remission was higher than that of HC group's, with no statistical significance, (P>0.05). The therapeutic efficacy in 69 de novo AL patients was evaluated, 45 AL patients achieved CR with a CR rate of 65.2%. cyclin H + AL patients CR rate (56.5%)is lower that of cyclin H - AL patients CR rate (82.6%).The CR rate difference was significantly (χ2=4.600,P<0.05). The therapeutic efficacy in 39 complete remission AL patients was evaluated. cyclin H + AL patients relapse rate (14.3%)is higher than that of cyclin H - AL patients (9.5%). The relapse rate had no statistical significance (χ2=0.286,P>0.05).For short of time is a renson of this result. 2 CDK7 mRNA both are positive in AL lines:HL60, K562. CDK7 mRNA was detected in some samples only. The rate and average expression level of CDK7 mRNA in de novo AL patients was(65.2%, 1.0612±0.5786); The positive rate and average expression level of CDK7 mRNA in relapsed patients was (84.6%, 1.1908±0.6863); The positive rate and average expression level of CDK7 mRNA in remission patients was (36.8%, 0.7532±0.1738); The positive rate and average expression level of CDK7 mRNA in healthy controls was (20%, 0.6453±0.2523); The CDK7 mRNA positive rates and expression levers in de novo AL patients and relapsed patients was higher than that of remission patients and healthy controls, (P<0.05). The positive rate and average expression lever of CDK7 mRNA in relapsed patients was higher than that of de novo AL patients and in complete remission was higher than that of HC group's, with no statistical significance, (P>0.05). The therapeutic efficacy in 69 de novo AL patients was evaluated, 45 AL patients achieved CR with a CR rate of 65.2%. CDK7 + AL patients CR rate (55.6%)is lower that of CDK7 - AL patients CR rate (83.3%). The CR rate was significantly (χ2=5.324,P<0.05). The therapeutic efficacy in 39 remission AL patients was evaluated. CDK7 + AL patients relapse rate (14.6%)is higher than that of CDK7 - AL patients CR rate (9.1%). The relapse rate had no statistical significance (χ2=0.397,P>0.05). It is possible for short time or rare relapse.3 In de novo AL patients , average expression level of cyclin H mRNA was positively correlated with CDK7 (r=0.388,P=0.009),The therapeutic efficacy in 35 AL patients was evaluated. The CR rate of cyclin H + CDK7 + group (51.4%) was lower than that of cyclin H - CDK7 - group (92.3%), T here was statistical significantly (χ2=6.759,P<0.05).4 In sex, age, WBC count classification, the difference of average expression levels of cyclin H, CDK7 had no statistical significance(P > 0.05 for all). In FAB classification, the difference of average expression levels of cyclin H, CDK7 in M2, M3, M4, M5 and L2 had no statistical significance(P>0.05 for all).5 In de novo AL patients, the levels of cyclin H, CDK7 was not correlated with CDK2/cyclin E2 (P>0.05), and cyclin H, CDK7 was negatively correlated with P53 (r=-0.122, r=-0.175, P>0.05) .There with no statistical significance.Conclusions:1 The positive rates and average expression levels of cyclin H, CDK7 mRNA in de novo AL patients and relapsed patients was significantly higher than that of complete remission and healthy controls. The CR rate of cyclin H +or CDK7+ group was lower than that of cyclin H -or CDK7- cases, indicating that cyclin H,CDK7 may be involved in the genesis and progression of AL. Its positive expression predicts poor prognosis.2 In AL patients, there was a positive correlation beween cyclin H and CDK7.The CR rate of cyclin H + CDK7 + group was lower than that of cyclin H + CDK7 - or cyclin H- CDK7 + group, and lower than that of cyclin H - CDK7- cases, indicating cyclin H and CDK7may be a complex .3 In AL patients, the level of CDK7/cyclin H was not correlated with CDK2/cyclin E2. we propose that CDK7/cyclin H can't improve mRNA and protein of CDK2/cyclin E2 but mainly phosphorylate them. The improvement of CDK7/cyclin H largely active CDK2/cyclin E2, enhance cell overcome G1/S.Thus they are important in AL progression.4 cyclin H, CDK7 was negatively correlated with P53, but had no statistical significance. P53 is a new substrate for the CDK7/cyclin H/Mat1 kinase complex. Under conditions when p53 gets activated, a downregulation of CAK kinase activity is only observed in the presence of a functional p53, the number of P53 is not clear. |
PDF Full Text Request