Clonal Evolution Enhances Leukemia-Propagating Cell Frequency in T Cell Acute Lymphoblastic Leukemia through Akt/mTORC1 Pathway Activation.
Document Type
Article
Publication Date
3-17-2014
JAX Source
Cancer Cell 2014 Mar 17; 25(3):366-78.
ISSN
1878-3686
PMID
24613413
Abstract
Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown molecular mechanisms. To address this issue, functional differences between single T cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model. Functional variation was observed within individual clones, with a minority of clones enhancing growth rate and leukemia-propagating potential with time. Akt pathway activation was acquired in a subset of these evolved clones, which increased the number of leukemia-propagating cells through activating mTORC1, elevated growth rate likely by stabilizing the Myc protein, and rendered cells resistant to dexamethasone, which was reversed by combined treatment with an Akt inhibitor. Thus, T-ALL clones spontaneously and continuously evolve to drive leukemia progression even in the absence of therapy-induced selection. Cancer Cell 2014 Mar 17; 25(3):366-78.
Recommended Citation
Blackburn J,
Liu S,
Wilder J,
Dobrinski K,
Lobbardi R,
Moore F,
Martinez S,
Chen E,
Lee C,
Langenau D.
Clonal Evolution Enhances Leukemia-Propagating Cell Frequency in T Cell Acute Lymphoblastic Leukemia through Akt/mTORC1 Pathway Activation. Cancer Cell 2014 Mar 17; 25(3):366-78.