The Expression Of S100A8and S100A9in Acute Myeloid Leukemia-Clinical And Experimental Study

Purpose: Calcium-binding proteins S100A8and S100A9have been increasinglyrecognized as biomarkers in various tumors. In this study, we investigated S100A8andS100A9expressions and their clinical implications in adult and children with acute myeloidleukemia （AML）.Methods: Two independent cohort of patients were retrospectively selected,including a cohort of189acute myeloid leukemia （AML） patients at different stages whoreceived intensive chemotherapy （AML-M3were excluded）（de novo=91, completeremission [CR]=64, relapse=34） from the first affiliated hospital of Soochow Universityduring2007to2011, and another cohort of50pediatric patients of AML （AML-M3wereexcluded）（de novo=30, CR=20） and52patients of acute lymphoid leukemia （ALL）（denovo=32, CR=20） at different stages from the children’s hospital of Soochow Universityduring2010to2012. Expression levels of S100A8and S100A9were detected in bonemarrow samples of the patients and20controls （adult=12, child=8） without leukemiausing real-time quantitative RT-PCR analysis.Results:（1）. In the cohort of189adult patients with AML, our results showed thatsignificantly positive correlations were detected between the expression levels of S100A8and S100A9in the patients at different the stages beeing measured. The expression levelsof S100A8and S100A9in de novo and relapse AML patients revealed no significantdifference (P_a8=0.257, P_a9=0.239), but were both lower than that in CR (P_a8 and a9<0.001)and control group (P_a8=0.0078, P_a9=0.0015). Patients with high expression levels of S100A8and S100A9frequently showed in AML with myelomonocytic differentiation （ie,France-American-British [FAB] classification: M4or M5）(P_a8=0.043, P_a9=0.013).S100A8overexpression was a predictor of inferior overall suvival （OS）（P=0.0012）. In amultivariate model for OS, high S100A8expression was a significant prognostic factortogether with age and bone marrow blast percentage （P=0.0087）. In the cytogeneticallyintermediate risk subgroup of de novo AML, S100A8high expression indicated relativelypoor therapeutic outcome （P=0.0012）. Although the expression level of S100A9couldn’tprovide marked prognostic value, S100A8/S100A9double high expression in de novoAML predicted shorter overall survival （P=0.013）. Multivariate analysis showed patientswith double high S100A8/S100A9expression also had shorter OS than those with lowexpression （P=0.003） after adjustment for age at diagnosis.（2）. Newly diagnosed pediatric patients with AML and ALL had significantly lowertranscript levels of S100A8and S100A9, comparing with patients in CR (P_a8=0.005andP_a9=0.004for AML, P_a8 and a9<0.001for ALL) and control group (P_a8 and a9<0.001forAML, P_a8=0.004and P_a9=0.005for ALL), moreover S100A8and S100A9expression inde novo AML were higher than in ALL (P_a8=0.0012and P_a9=0.05). In the small size ofAML, high S100A9expression level predicted relatively unfavorable early treatmentoutcome (P_a9=0.025), S100A8expression showed the same trend but did not reachstatistic significance (P_a8=0.06). On the contrary, S100A8and S100A9expression levelshad no efficiency to predict early treatment outcome in ALL patients considering theresponses of corticosteroid pretreatment and induction chemotherapy.Conclusion: Our results demonstrated that the expressions of S100A8and S100A9were signifiantly associated with the progression of AML and ALL. High S100A8expression emerged as a negative prognostic factor and provided information in addition toestablished cytogenetic risk factors, refining the stratification of adult de novo AML.S100A8/S100A9double expression level in adult de novo AML patients providedprognostic values. S100A8and S100A9expression levels showed positive correlation withthe clinical status in pediatric acute leukemia, especially, in de novo AML, they canpotentially be markers for predicting early therapeutic efficacy. Purpose: The aim of this study was to construct retroviral vectors carrying the genesencoding calcium-binding proteins S100A8and S100A9, which provides an effectiveplatform for exploring the function of thess genes in leukemia.Methods: After digestion by different restriction endonucleases, the S100A8andS100A9genes were recombined with the transfer plasmids, respectively.Results: The sequences of cloned S100A8and S100A9genes were the same as that inGenBank. The size of products restricted by EcoRⅠand XhoⅠas well as HpaⅠand XhoⅠwere the same as the predicted ones.Conclusion: The retroviral vectors carrying S100A8and S100A9genes have beensuccessfully constructed which makes it possible for exploring function of S100A8andS100A9in leukemic cells.