TY - JOUR
T1 - Posttranslational regulation of self-renewal capacity
T2 - insights from proteome and phosphoproteome analyses of stem cell leukemia
AU - Trost, Matthias
AU - Sauvageau, Martin
AU - Hérault, Olivier
AU - Deleris, Paul
AU - Pomiès, Christelle
AU - Chagraoui, Jalila
AU - Mayotte, Nadine
AU - Meloche, Sylvain
AU - Sauvageau, Guy
AU - Thibault, Pierre
PY - 2012/8/23
Y1 - 2012/8/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865444387&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-12-397844
DO - 10.1182/blood-2011-12-397844
M3 - Article
C2 - 22802335
SN - 1528-0020
VL - 120
SP - e17-27
JO - Blood
JF - Blood
IS - 8
ER -