Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy

Abstract

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.

Identification of Prolificacy‐Related Differentially Expressed Proteins from Sheep (Ovis aries) Hypothalamus by Comparative Proteomics

“…In our comparison of PL versus ML, the top two differentially abundant proteins were bcl‐2‐associated athanogene 4 (BAG4) and insulin‐like growth factor‐1 receptor (IGF1R). BAG4, also called silencer of death domains (SODD), has been shown to have crucial roles in inhibiting apoptosis . Even though no pathway was annotated, IGF1R was also enriched in GO terms associated with apoptosis, such as negative regulation of apoptotic process, which implied that anti‐apoptotic activities may play an important role in the luteal phase.…”

Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells

“…This burden is partly due to uncontrolled cell proliferation and poor response to chemotherapy in adult patients [4]. Leukemic cells abnormally express numerous genes that are associated with proliferation and apoptosis compared to normal hematopoietic cells, and these genes are thought to be the main cause of drug resistance [5]. An examination of abnormally expressed genes in leukemic cells, and of the pathogenic mechanisms associated with these genes, would therefore have great value for the development of targeted therapies.…”

The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia

“…BAG4 influences the growth of several types of cancer, such as pancreatic [24] , ovarian [25] , and breast cancer [26] . Additionally, Cisterne [27] and Tao [28] found that in acute lymphoblastic leukemia, BAG4/SODD plays the important role in various processes, including apoptosis and the chemotherapy sensitivity. We predicted and verified that BAG4 is a direct targets of miR-1-3p and may be a key factor in BEZ235-induced apoptosis.…”