Редактирование: DLAT (раздел)

==Publications==

{{medline-entry
|title=Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29196338
|abstract=B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, is still essentially incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. A comprehensive proteome analysis of primary human B-CLL cells and B cells from younger as well as elderly healthy donors was performed. For comparison, the chronic B cell leukemia cell line JVM-13 was also included. A principal component analysis comprising 6,945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and B-CLL patients, while identifying JVM-13 as poorly related cells. Mass spectrometric proteomics data have been made fully accessible via ProteomeXchange with identifier PXD006570-PXD006572, PXD006576, PXD006578, and PXD006589-PXD006591. Remarkably, B cells from aged controls displayed significant regulation of proteins related to stress management in mitochondria and ROS stress such as [[DLAT]], [[FIS1]], and [[NDUFAB1]], and DNA repair, including [[RAD9A]], [[MGMT]], and [[XPA]]. ROS levels were indeed found significantly increased in B cells but not in T cells or monocytes from aged individuals. These alterations may be relevant for tumorigenesis and were observed similarly in B-CLL cells. In B-CLL cells, some remarkable unique features like the loss of tumor suppressor molecules [[PNN]] and [[JARID2]], the stress-related serotonin transporter [[SLC6A4]], and high expression of [[ZNF207]], [[CCDC88A]], [[PIGR]] and [[ID3]], otherwise associated with stem cell phenotype, were determined. Alterations of metabolic enzymes were another outstanding feature in comparison to normal B cells, indicating increased beta-oxidation of fatty acids and increased consumption of glutamine. Targeted metabolomics assays corroborated these results. The present findings identify a potential proteome signature for immune senescence in addition to previously unrecognized features of B-CLL cells and suggest that aging may be accompanied by cellular reprogramming functionally relevant for predisposing B cells to transform to B-CLL cells.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* B-Lymphocytes
* Cell Line, Tumor
* Female
* Humans
* Leukemia, Lymphocytic, Chronic, B-Cell
* Male
* Metabolomics
* Middle Aged
* Neoplasm Proteins
* Proteomics

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795392
}}