Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma

Author:

Ben-Batalla Isabel12,Schultze Alexander12,Wroblewski Mark12,Erdmann Robert12,Heuser Michael3,Waizenegger Jonas S.12,Riecken Kristoffer4,Binder Mascha1,Schewe Denis5,Sawall Stefanie12,Witzke Victoria12,Cubas-Cordova Miguel12,Janning Melanie12,Wellbrock Jasmin1,Fehse Boris4,Hagel Christian6,Krauter Jürgen3,Ganser Arnold3,Lorens James B.7,Fiedler Walter1,Carmeliet Peter89,Pantel Klaus2,Bokemeyer Carsten1,Loges Sonja12

Affiliation:

1. Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

2. Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

3. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;

4. Research Department Cell and Gene Therapy, Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

5. Department of Pediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany;

6. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

7. Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway;

8. Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, VIB, Leuven, Belgium; and

9. Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, Katholieke Universiteit Leuven, Leuven, Belgium

Abstract

Key PointsAxl inhibition by BGB324 is active in FLT3-mutated and FLT3 wild-type AML, and presence of Axl and Gas6 are required for therapeutic efficacy. AML cells educate BMDSCs to secrete Gas6, which mediates leukemia cell proliferation and therapy resistance.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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