ITEM METADATA RECORD
Title: Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma
Authors: Ben-Batalla, Isabel ×
Schultze, Alexander
Wroblewski, Mark
Erdmann, Robert
Heuser, Michael
Waizenegger, Jonas S
Riecken, Kristoffer
Binder, Mascha
Schewe, Denis
Sawall, Stefanie
Witzke, Victoria
Cubas-Cordova, Miguel
Janning, Melanie
Wellbrock, Jasmin
Fehse, Boris
Hagel, Christian
Krauter, Jürgen
Ganser, Arnold
Lorens, James B
Fiedler, Walter
Carmeliet, Peter
Pantel, Klaus
Bokemeyer, Carsten
Loges, Sonja #
Issue Date: Oct-2013
Publisher: W.B. Saunders
Series Title: Blood vol:122 issue:14 pages:2443-2452
Abstract: Acute myeloid leukemia (AML) represents a clonal disease of hematopoietic progenitors characterized by acquired heterogenous genetic changes that alter normal mechanisms of proliferation, self-renewal, and differentiation.(1) Although 40% to 45% of patients younger than 65 years of age can be cured with current therapies, only 10% of older patients reach long-term survival.(1) Because only very few novel AML drugs were approved in the past 2 decades, there is an urgent need to identify novel targets and therapeutic strategies to treat underserved AML patients. We report here that Axl, a member of the Tyro3, Axl, Mer receptor tyrosine kinase family,(2-4) represents an independent prognostic marker and therapeutic target in AML. AML cells induce expression and secretion of the Axl ligand growth arrest-specific gene 6 (Gas6) by bone marrow-derived stromal cells (BMDSCs). Gas6 in turn mediates proliferation, survival, and chemoresistance of Axl-expressing AML cells. This Gas6-Axl paracrine axis between AML cells and BMDSCs establishes a chemoprotective tumor cell niche that can be abrogated by Axl-targeting approaches. Axl inhibition is active in FLT3-mutated and FLT3 wild-type AML, improves clinically relevant end points, and its efficacy depends on presence of Gas6 and Axl. Axl inhibition alone or in combination with chemotherapy might represent a novel therapeutic avenue for AML.
URI: 
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science