Posttranslational regulation of self-renewal capacity: insights from proteome and phosphoproteome analyses of stem cell leukemia

作者：Trost Matthias; Sauvageau Martin; Herault Olivier; Deleris Paul; Pomies Christelle; Chagraoui Jalila; Mayotte Nadine; Meloche Sylvain; Sauvageau Guy^*; Thibault Pierre

来源：Blood, 2012, 120(8): E17-E27.

DOI：10.1182/blood-2011-12-397844

We recently generated 2 phenotypically similar Hoxa9+ Meis1 overexpressing acute myeloid leukemias that differ by their in vivo biologic behavior. The first leukemia, named FLA2, shows a high frequency of leukemia stem cells (LSCs; 1 in 1.4 cells), whereas the second, FLB1, is more typical with a frequency of LSCs in the range of 1 per several hundred cells. To gain insights into possible mechanisms that determine LSC self-renewal, we profiled and compared the abundance of nuclear and cytoplasmic proteins and phosphoproteins from these leukemias using quantitative proteomics. These analyses revealed differences in proteins associated with stem cell fate, including a hyperactive p38 MAP kinase in FLB1 and a differentially localized Polycomb group protein Ezh2, which is mostly nuclear in FLA2 and predominantly cytoplasmic in FLB1. Together, these newly documented proteomes and phosphoproteomes represent a unique resource with more than 440 differentially expressed proteins and 11 543 unique phosphopeptides, of which 80% are novel and 7% preferentially phosphorylated in the stem cell-enriched leukemia. (Blood. 2012;120(8):e17-e27)

• 出版日期2012-8-23