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

Matthias Trost (Lead / Corresponding author), Martin Sauvageau, Olivier Hérault, Paul Deleris, Christelle Pomiès, Jalila Chagraoui, Nadine Mayotte, Sylvain Meloche, Guy Sauvageau (Lead / Corresponding author), Pierre Thibault (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)e17-27
    Number of pages11
    JournalBlood
    Volume120
    Issue number8
    Early online date16 Jul 2012
    DOIs
    Publication statusPublished - 23 Aug 2012

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