Diagenode

Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors.


Booth CAG, Barkas N, Neo WH, Boukarabila H, Soilleux EJ, Giotopoulos G, Farnoud N, Giustacchini A, Ashley N, Carrelha J, Jamieson L, Atkinson D, Bouriez-Jones T, Prinjha RK, Milne TA, Teachey DT, Papaemmanuil E, Huntly BJP, Jacobsen SEW, Mead AJ

Lympho-myeloid restricted early thymic progenitors (ETPs) are postulated to be the cell of origin for ETP leukemias, a therapy-resistant leukemia associated with frequent co-occurrence of EZH2 and RUNX1 inactivating mutations, and constitutively activating signaling pathway mutations. In a mouse model, we demonstrate that Ezh2 and Runx1 inactivation targeted to early lymphoid progenitors causes a marked expansion of pre-leukemic ETPs, showing transcriptional signatures characteristic of ETP leukemia. Addition of a RAS-signaling pathway mutation (Flt3-ITD) results in an aggressive leukemia co-expressing myeloid and lymphoid genes, which can be established and propagated in vivo by the expanded ETPs. Both mouse and human ETP leukemias show sensitivity to BET inhibition in vitro and in vivo, which reverses aberrant gene expression induced by Ezh2 inactivation.

Tags
Antibody

Share this article

Published
February, 2018

Source

Products used in this publication

  • Antibody ChIP-seq grade icon
    C15410196
    H3K27ac polyclonal antibody - Premium

Events

 See all events

News

 See all news


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.



  ABOUT SSL CERTIFICATES

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics