| ObjectiveMultiple myeloma (MM) is a type of hematological malignancy. Althoughintensive chemotherapy with steroids, melphalan and thalidomide, stem celltransplantation, and recently the advent of targeted therapy such as proteasomeinhibitors (bortezomib lenalidomide) help to decrease the signs and symptoms ofdisease, MM still remains a debilitating, incurable disease. Therefore, further studies inthe pathogenesis of MM especially from a genetic point of view is warranted, topromote understanding in the disease occurrence and development, and to provide thebasis for treatment of this disease. The elevated telomerase is associated withimmortalized of tumor. The dynamic changes of telomere length associated withoncogenesis, so the roles of the telomere/telomerase system in tumor genesis havereceived much more attention recently. The expression of hTERT mRNA is therate-limiting factor for the telomerase activation. The aim of this study is to inves-tigate the expression of hTERT mRNA and the changes of telomere length in order tounderstand its functional role in disease pathogenesis and development MM, and also todetermine the correlation between telomeres-telomerase system and β2-microglobulinlevels which is closely related to disease prognosis and disease stage.Methods:We selected and evaluated30patients with MM admitted in HematologyDepartment of First Affiliated hospital of Dalian Medical University from January2009to October2011. The diagnosis and treatment of MM was conformed according to<diagnosis and treatment standards of hematology> of the third edition which edited byZhang Zhi Nan. The patients were further categorized into3subgroups: firstly thenewly diagnosed16cases, secondly the remission group9cases (CR or VGPR), and finally the relapsed group5cases. The frequency of myeloma cell in newly diagnosedgroup and relapsed group ranged from15.5%to48%. In addition,10bone marrowbiopsy specimens of patients with non-neoplastic disease, such as iron deficiencyanemia, megaloblastic anemia and fever were used as the control group. We extractedbone marrow mononuclear cells from all the cases. Quantitative real-time PCR(Q-PCR) was used to detect hTERT mRNA expression and telomere length from bonemarrow mononuclear cells in both the MM and control groups. β2-microglobulin wasalso collected and studied to find correlation with the hTERT mRNA expression andtelomere length in MM. The result was analyzed by statistical software SPSS16.0.Results:1. The expression of hTERT mRNA in newly diagnosed group (3.05±0.58) wassignificantly higher than the control group (1.49±0.38)(P<0.05);*The expression of hTERT mRNA in relapsed group (3.19±0.61) and in newlydiagnosed group (3.05±0.58) was significantly higher than the remission group (1.79±0.21)(P<0.05);*There was no significant difference between relieved group (1.79±0.21) andcontrol group (1.49±0.38) about the expression of hTERT mRNA (P>0.05);*There was no significant difference between relapsed group and newly diagnosedgroup (P>0.05).2. The telomere length of newly diagnosed group (1.67±0.29) was significantlyshorter than control group (2.81±0.37)(P<0.05);*The telomere length of newly diagnosed (1.67±0.29) and relapsed group(1.57±0.41) was significantly shorter than remission group (2.62±0.46)(P<0.05);*There was no significant difference between remission group (2.62±0.46) andcontrol group (2.81±0.37) about telomere length (P>0.05);*There was no significant difference between newly diagnosed group (1.67±0.29)and relapsed group (1.57±0.41) about telomere length (P>0.05).3. We analyzed the correlation of telomere length and hTERT-mRNA in30patients with MM. The expression of hTERT-mRNA was negatively associated withtelomere length (r=-0.514, P<0.05).4.We studied the correlation of β2-microglobulin, hTERT-mRNA expression andtelomere length respectively. The expression of hTERT-mRNA was positivelyassociated withβ2-microglobulin(r=0.481, P<0.05); The telomere length was negativelyassociated with β2-microglobulin(r=-0.470, P<0.05). Conclusion:1. The expression of hTERT mRNA in the newly diagnosed group was signific-antly higher than control group, relapsed group and newly diagnosed was significantlyhigher than remission group. There was no significant difference between relapsed andnewly diagnosed group about hTERT mRNA. So hTERT mRNA was not only involvedin pathogenesis of MM, but was also related to disease activity states.2. Telomere length in newly diagnosed was significantly shorter than control group.There was probable that genome was unstable in the pathogenesis of MM. Telomerelength in newly diagnosed and relapsed group was significantly shorter than remissiongroup. There was no significant difference between relapsed group and newlydiagnosed group about telomere length. Telomere length may help to determine thedisease activity states.3. The expression of hTERT mRNA was negatively associated with telomerelength in MM. Telomere length may influence telomerase activity in MM pathogenesis.4. The expression of hTERT mRNA was positively associatedwithβ2-microglobulin, The telomere length was negatively associated withβ2-microglobulin. hTERT mRNA and telomere length can be used as an indicators forthe prognosis of patient and clinical stage in MM. |
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