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

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

in: BLOOD, Jahrgang 122, Nr. 14, 03.10.2013, S. 2443-52.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Ben Batalla, I, Schultze, A, Wroblewski, M, Erdmann, R, Heuser, M, Waizenegger, JS, Riecken, K, Binder, M, Schewe, D, Sawall, S, Witzke, V, Cubas Cordova, M, Janning, M, Wellbrock, J, Fehse, B, Hagel, C, Krauter, J, Ganser, A, Lorens, JB, Fiedler, W, Carmeliet, P, Pantel, K, Bokemeyer, C & Loges, S 2013, 'Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma', BLOOD, Jg. 122, Nr. 14, S. 2443-52. https://doi.org/10.1182/blood-2013-03-491431

APA

Ben Batalla, I., Schultze, A., Wroblewski, M., Erdmann, R., Heuser, M., Waizenegger, J. S., Riecken, K., Binder, M., Schewe, D., Sawall, S., Witzke, V., Cubas Cordova, M., Janning, M., Wellbrock, J., Fehse, B., Hagel, C., Krauter, J., Ganser, A., Lorens, J. B., ... Loges, S. (2013). Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma. BLOOD, 122(14), 2443-52. https://doi.org/10.1182/blood-2013-03-491431

Vancouver

Ben Batalla I, Schultze A, Wroblewski M, Erdmann R, Heuser M, Waizenegger JS et al. Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma. BLOOD. 2013 Okt 3;122(14):2443-52. https://doi.org/10.1182/blood-2013-03-491431

Bibtex

@article{97490a3c24824ea59aa9152d198a8a2c,
title = "Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma",
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.",
keywords = "Animals, Antineoplastic Agents, Blotting, Western, Bone Marrow Cells, Clinical Trials as Topic, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Humans, Intercellular Signaling Peptides and Proteins, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute, Male, Mice, Paracrine Communication, Prognosis, Proto-Oncogene Proteins, Real-Time Polymerase Chain Reaction, Receptor Cross-Talk, Receptor Protein-Tyrosine Kinases, Stromal Cells, Xenograft Model Antitumor Assays",
author = "{Ben Batalla}, Isabel and Alexander Schultze and Mark Wroblewski and Robert Erdmann and Michael Heuser and Waizenegger, {Jonas S} and Kristoffer Riecken and Mascha Binder and Denis Schewe and Stefanie Sawall and Victoria Witzke and {Cubas Cordova}, Miguel and Melanie Janning and Jasmin Wellbrock and Boris Fehse and Christian Hagel and J{\"u}rgen Krauter and Arnold Ganser and Lorens, {James B} and Walter Fiedler and Peter Carmeliet and Klaus Pantel and Carsten Bokemeyer and Sonja Loges",
year = "2013",
month = oct,
day = "3",
doi = "10.1182/blood-2013-03-491431",
language = "English",
volume = "122",
pages = "2443--52",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "14",

}

RIS

TY - JOUR

T1 - Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma

AU - Ben Batalla, Isabel

AU - Schultze, Alexander

AU - Wroblewski, Mark

AU - Erdmann, Robert

AU - Heuser, Michael

AU - Waizenegger, Jonas S

AU - Riecken, Kristoffer

AU - Binder, Mascha

AU - Schewe, Denis

AU - Sawall, Stefanie

AU - Witzke, Victoria

AU - Cubas Cordova, Miguel

AU - Janning, Melanie

AU - Wellbrock, Jasmin

AU - Fehse, Boris

AU - Hagel, Christian

AU - Krauter, Jürgen

AU - Ganser, Arnold

AU - Lorens, James B

AU - Fiedler, Walter

AU - Carmeliet, Peter

AU - Pantel, Klaus

AU - Bokemeyer, Carsten

AU - Loges, Sonja

PY - 2013/10/3

Y1 - 2013/10/3

N2 - 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.

AB - 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.

KW - Animals

KW - Antineoplastic Agents

KW - Blotting, Western

KW - Bone Marrow Cells

KW - Clinical Trials as Topic

KW - Disease Models, Animal

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Humans

KW - Intercellular Signaling Peptides and Proteins

KW - Kaplan-Meier Estimate

KW - Leukemia, Myeloid, Acute

KW - Male

KW - Mice

KW - Paracrine Communication

KW - Prognosis

KW - Proto-Oncogene Proteins

KW - Real-Time Polymerase Chain Reaction

KW - Receptor Cross-Talk

KW - Receptor Protein-Tyrosine Kinases

KW - Stromal Cells

KW - Xenograft Model Antitumor Assays

U2 - 10.1182/blood-2013-03-491431

DO - 10.1182/blood-2013-03-491431

M3 - SCORING: Journal article

C2 - 23982172

VL - 122

SP - 2443

EP - 2452

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 14

ER -