title: Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy.
abstract: This study explored the clinical significance of silencer of death domain (SODD) expression in childhood acute lymphoblastic leukemia (ALL) and its influence on chemotherapy as well as the effect of SODD expression on apoptosis of leukemic cells. The expression of SODD proteins in different ALL groups was determined by immunocytochemistry. The SODD RNAi-interfering plasmid was constructed and transferred to Jurkat cells, and the effects of SODD expression on cell proliferation and apoptosis were analyzed using the MTT and FCM methods. The expressions of SODD, Phospho-NF-κB-P65, Bcl-2, and Caspase 3 were detected by Western blot analysis. The expression of SODD proteins was significantly higher in the ALL groups than in the control group (P < 0.05). The positive expression rate of SODD was significantly higher in refractory/relapsed and clinical high-risk groups than in standard-risk, initial treatment, and complete remission groups (P < 0.05). Microtubule-targeting drugs such as vincristine and taxol can notably down-regulate SODD expression during apoptosis, whereas DNR, and Ara-c cannot. The sensitivity of Jurkat cells to chemotherapeutic drugs increased with down-regulated SODD expression induced by SODD-interfering plasmid transfection. The sensitivity of the cells transfected with SODD-cloning genes decreased. SODD expression was high in the ALL children. These findings indicated that SODD over-expression might be correlated with the clinical classification, curative effect, and prognosis of ALL cells. Microtubule-targeting drugs can specifically down-regulate SODD expression in leukemic cells, thereby increasing the sensitivity of leukemic cells to SODD-targeting chemotherapeutics. In contrast, increased SODD expression tends to reduce sensitivity.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: H F
authors.initials: HF
authors.lastname: Tao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China yuanshengliucn@126.com.
authors.forename: Y S
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Fang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Su
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: F H
authors.initials: FH
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Y S
authors.initials: YS
authors.lastname: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C116906:BAG4 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2