| PurposeTo Assess quality of life(QoL)and symptom burden in patients with primary myelofibrosis(PMF),analyze associations between psychosocial factors,clinical features and patients' QoL.To investigate the potential role of stress in the pathogenesis of PMF by cell study in vitro.Materials and Methods1.The Chinese version of MPN-SAF TSS and SF-36 form(SF-36)Health Survey were used to measure health-related QoL of 149 patients enrolled in our cross-sectional study.Social characteristics,clinical features of patients were collected to disclose possible correlation.2.Adrenaline was administrated to treat chronic myeloid cell K562 in vitro to stimulate chronic myeloid cell K562,as well as alpha and beta blockers of adrenoreceptors.Jak-stat signaling pathway related molecules were tested after "stress"stimulation.CCK8 assay was used to evaluate cell viability.Protein expression was evaluated by Western blot.RT-PCR was used to test mRNA levels of related genes.Results1.133 in 149 patients completed the questionnaire.The total symptom burden of PMF patients was 25.3 ± 17.2(0-100),and the most common symptom reported was fatigue,with comparatively heavier symptoms being fatigue(4.3 ± 2.7),decreased activity(3.9±3.0),and abdominal discomfort(3.0±3.0).2.PMF patients experienced a significant reduction in QoL on different aspect according to their age group,which was lower than the norm(p<0.05),showing poor score on Role Physical(RP),Role Emotional(RE)and General Health(GH).Univariate analysis showed living in rural areas(P<0.01),heavy symptom burden(P<0.01),JAK2V617F mutation(P<0.05),transfusion dependence(P<0.05)predicted a poorer overall quality of life.In addition to symptom burden and transfusion dependence,anemia and living in rural areas also predicted lower Physical Component Summary Scale.There was a significant difference in symptom burden between the high-scale group and the low-scale group(with a cut-off of 50)(P<0.01),while risk stratification.in both groups were comparable.Multivariate analysis further confirmed the above results.3.In vitro experiment showed that adrenaline(10nmol/L,48h)stimulated the proliferation of K562 cells,a chronic myeloid tumor cells.The proliferation rate reached to 156%±26.9%(p<0.05),153%±25.9%(p<0.05)at 100nm and 1um respectively.(1)Epinephrine promoted K562 cells proliferation by activating alpha,beta adrenoreceptors,including both isoprenaline(100 nmol/L or higher,48 h)and norepinephrine(100 nmol/L or higher,24 h).K562 proliferation rates significantly increased to 124.2%±6.0%(p<0.05),125.9%±9.7%(p<0.05),136.9%±4.9%(p<0.01)with norepinephrine at 100 nm,1 um,10um after 24 h.The proliferation rates increased to 132%±11.79%(p<0.05)with isoprenaline at 100nm after 48h.(2)From the other side,phentolamine(100 umol/L or higher,24 h),propranolol(10 umol/L or higher,24 h),metoprolol(10 umol/L or higher,48 h)inhibited cell proliferation.K562 proliferation rates significantly dropped to 80.1%± 2.7%(p<0.01)with phentolamine at 100um after 24h,to 83.2%±4.4%(p<0.05),47.67%±1.1%(p<0.01)with propranolol at 10um,100um after 24h.The proliferation rates decreased to 34.1%±5.9(p<0.01)and 23.1%±2.3%(p<0.01)with metoprolol at 10um,100um after 48h.(3)Low-dose adrenaline exposure for a longer period(?1 nm,14 d)also promoted K562 proliferation at 1 nmol/L-100 nmol/L after 14 d continuous treatment with a proliferation rate of 117.6%± 13.0%(p<0.01),127.2%±11.29%(p<0.01).Similarly,propranolol(?20 nm,14 d)inhibited cell viability at 20 nmol/L,100 nmol/L after 14 d exposure.The proliferation rates were 58.0± 13.0%(p<0.01)and 36.4%± 7.3%(p<0.01)respectively.(4)Epinephrine up-regulated the expression of STAT3 mRNA in K562 cells,whereas mRNA levels of JAK2 and SOCS3 remained unchanged.ConclusionHigher symptom burden(MPN-SAF TSS?22),JAK2V617F mutation,transfusion dependence and living in rural areas are risk factors for poor quality of life in PMF patients.In vitro experiments showed that stress could be a potential stimulating factor of the development of chronic myeloid tumor. |
PDF Full Text Request