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- W1841270877 abstract "CLL is a malignant disease of B-cells characterised by a heterogeneousclinical outcome. Some patients require an early treatment and have lowsurvival time, while others never need treatment. Many prognostic markershave been established and used to help predict the clinical course of CLL.Despite advances in understanding the biology of CLL, the moleculardifferences underlying the variable clinical outcome of CLL are not yet fullyunderstood.The hypothesis of this study was that the heterogeneous outcome ofCLL could be driven, in part, by the aberrant expression of proteins in the twoforms of CLL. Therefore, this study aimed to identify these proteins usingproteomics approaches.In an attempt to achieve this goal, four steps were performed. Firstly, acellular fractionation method was developed to extract cellular proteins into twodifferent fractions (NP40 fraction for cytosolic protein enrichment and SDSfraction for nuclear protein enrichment).Secondly, extracted proteins were subjected to qualitative proteomicsanalysis using 2D nano-LC and MALDI TOF-TOF mass spectrometry in orderto identify CLL proteins. Integrating the identified proteins (n=900) withpreviously published transcriptome of CLL cells and normal B-cells highlighted20 proteins with preferential expression in CLL cells - some of which werelinked to human cancer.Thirdly, iTRAQ technology coupled with 2D nano-LC and MALDI TOFTOFmass spectrometry was used to measure the relative expression ofproteins in different CLL samples. This workflow identified 15 altered proteinsin the two forms of CLL and detected 14 proteins with variable expression.Finally, six proteins were selected for investigation in an additional CLLcohort. Of these proteins thyroid hormone receptor-associated protein 3(TR150), T-cell leukaemia/lymphoma protein 1A (TCL-1) and S100A8 showedassociation with poor prognosis CLL and early requirement for treatment.Additionally, myosin-9 exhibited reduced expression in poor prognosis CLLsamples.!!Overall, this study identified proteins with potential importance in CLLprognosis and pathology. These proteins merit investigation in a larger CLLcohort to further confirm their relevance to CLL. In addition, this study showedthe usefulness of combining cellular fractionation with proteomics andtranscriptomics to identify proteins with potential role in CLL." @default.
- W1841270877 created "2016-06-24" @default.
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- W1841270877 date "2013-01-01" @default.
- W1841270877 modified "2023-09-27" @default.
- W1841270877 title "Proteomics analysis of chronic lymphocytic leukaemia cells" @default.
- W1841270877 hasPublicationYear "2013" @default.
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