natural compound library Information As Well As The IllInformed BeliefsOver the past 50 years, the prognosis for pediatric...
ALL cell lines have similar expression levels of total survivin. In addition, the expressionpatterns of survivin among cel...
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natural compound library Information As Well As The Ill Informed Beliefs

Published on: Mar 3, 2016
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  • 1. natural compound library Information As Well As The IllInformed BeliefsOver the past 50 years, the prognosis for pediatric acute lymphoblastic leukemia (ALL) haschanged from a terminal diagnosis to a treatable disease.1 The success of currenttherapeutic regimens has given rise to the identification of a subset of patients who will haverecurrent or refractory disease. Unfortunately, patients within these subsets have highlyresistant disease that may not be overcome even with myeloablative therapy andhematopoietic stem cell transplant. These diseases may have approached the limit oftreatment by standard chemotherapeutic regimens. Therefore, new targets for therapy areimperative in the hope of improving outcomes. A report from the Childrens Oncology Grouphas shown a differential expression profile of relapsed ALL compared with initial diagnosis.2One of the genes showing a marked increase in expression in patients with recurrent diseaseis survivin (aka BIRC5). Survivin is an attractive target for therapy because it is expressedmainly during development and in the setting ofCorrespondence: Dr BH Chang, Division of Hematology and Oncology, Department ofPediatrics, OHSU Knight Cancer Institute, Mailcode CDRCP, 3181 SW Sam Jackson ParkRoad, Portland, OR, USA. E-mail: changb@ohsu.edu Received 5 February 2011; revised 10July 2011; accepted 11 August 2011; published online 30 September 2011malignancy with little to no expression in normal terminally differentiated tissue. Furthermore,survivin overexpression has correlated with resistant and refractory disease in many differentmalignancies including ALL.3 Survivin is a small 16 kD protein that belongs to the inhibitor ofapoptosis (IAP) family and also functions as a member of the chromosome passengercomplex. Survivin is a unique member of the IAPs in that it is both the smallest member andmay not directly interact with caspases. Instead, it may interact with another IAP,smac/Diablo, to regulate apoptosis within the mitochondria.4 Transcription of survivin showsseveral splice variants with conserved N-terminal domains, with most of the divergenceoccurring within or after the baculovirus IAP repeat domain.5? Recent published reportswould suggest that these splice variants may have different subcellular localization includingthe mitochondria and different apoptotic activities.8 The role of survivin as a member of thechromosome passenger complex, in which it plays a critical role during mitosis, is betterdefined.9 As such, survivin expression is cellcycle dependent, with the highest expressionduring G2/M through canonical cell cycle-dependent and cell-cycle homology regions withinthe proximal promoter.10 During mitosis, survivin specifically localizes with INCENP andAurora B kinase within the mitotic apparatus from the centromeres in prophase, kinetochoresin metaphase, the mid-plate during anaphase and the mid-body during cytokinesis.Furthermore, it is the direct interaction of survivin with both Aurora B kinase and INCENP thatis essential for cell division.11?3 Survivin phosphorylation at Ser 20 by PLK1 (polo-likekinase) is required for the priming of Aurora B kinase activity to undergo cell division.14 Inthis study we verified the cell-cycle dependence of survivin expression within pediatric ALLcells. We further tested whether several pediatric leukemic cell lines as well as primarypatient samples were sensitive to manipulation of survivin expression and activity. Pediatric
  • 2. ALL cell lines have similar expression levels of total survivin. In addition, the expressionpatterns of survivin among cell lines were similar with an increase in survivin expressionduring G2/M. natural compound library Info And Also Urban Myths, natural compound libraryInformation Plus Urban Myths, natural compound library Information And Facts As Well AsThe Urban Myths

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