Phenotypically Dormant and Immature Leukaemia Cells Display Increased Ribosomal Protein S6 PhosphorylationReport as inadecuate




Phenotypically Dormant and Immature Leukaemia Cells Display Increased Ribosomal Protein S6 Phosphorylation - Download this document for free, or read online. Document in PDF available to download.

Mechanistic-mammalian target of rapamycin mTOR activity drives a number of key metabolic processes including growth and protein synthesis. Inhibition of the mTOR pathway promotes cellular dormancy. Since cells from patients with acute myeloid leukaemia AML can be phenotypically dormant quiescent, we examined biomarkers of their mTOR pathway activity concurrently with Ki-67 and CD71 indicators of cycling cells by quantitative flow cytometry. Using antibodies to phosphorylated epitopes of mTOR S2448 and its downstream targets ribosomal protein S6 rpS6, S235-236 and 4E-BP1 T36-45, we documented that these phosphorylations were negligible in lymphocytes, but evident in dormant as well as proliferating subsets of both mobilised normal stem cell harvest CD34+ cells and AML blasts. Although mTOR phosphorylation in AML blasts was lower than that of the normal CD34+ cells, p-4E-BP1 was 2.6-fold higher and p-rpS6 was 22-fold higher. Moreover, in contrast to 4E-BP1, rpS6 phosphorylation was higher in dormant than proliferating AML blasts, and was also higher in the immature CD34+CD38- blast subset. Data from the Cancer Genome Atlas show that rpS6 expression is associated with that of respiratory chain enzymes in AML. We conclude that phenotypic quiescence markers do not necessarily predict metabolic dormancy and that elevated rpS6 ser235-236 phosphorylation is characteristic of AML.



Author: Monica Pallis , Tamsin Harvey, Nigel Russell

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents