Axl inhibition: a potential road to a novel acute myeloid leukemia therapy?
作者： Melanie Janning , Isabel Ben-Batalla , Sonja Loges
DOI: 10.1586/17474086.2015.997704
关键词:
摘要: Novel treatment options in acute myeloid leukemia (AML) are urgently needed; has not changed significantly over the past decades and survival is still dismal, especially elderly patients. Axl, a member of Tyro3, Mer (TAM) receptor family, mediates proliferation AML cells upregulated upon cytostatic treatment. In addition, induce expression Axl ligand growth arrest-specific gene 6 (Gas6) bone marrow stroma cells, which further amplifies their therapy resistance. Interruption signaling by pharmacological approaches, including small molecule inhibitor BGB324, decreased disease burden prolonged mice. The Gas6-Axl pathway translational relevance because expressed approximately 50% patients Axl-targeting approaches can block primary human cells. Thus, represents potential novel target BGB324 now clinical development.
informahealthcare.com参考文章(26)
A B Lee-Sherick, K M Eisenman, S Sather, A McGranahan, P M Armistead, C S McGary, S A Hunsucker, J Schlegel, H Martinson, C Cannon, A K Keating, H S Earp, X Liang, D DeRyckere, D K Graham, Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia Oncogene. ,vol. 32, pp. 5359- 5368 ,(2013) , 10.1038/ONC.2013.40
S P Whitman, J Kohlschmidt, K Maharry, S Volinia, K Mrózek, D Nicolet, S Schwind, H Becker, K H Metzeler, J H Mendler, A-K Eisfeld, A J Carroll, B L Powell, T H Carter, M R Baer, J E Kolitz, I-K Park, R M Stone, M A Caligiuri, G Marcucci, C D Bloomfield, GAS6 expression identifies high-risk adult AML patients: potential implications for therapy. Leukemia. ,vol. 28, pp. 1252- 1258 ,(2014) , 10.1038/LEU.2013.371
J Boysen, S Sinha, T Price-Troska, S L Warner, D J Bearss, D Viswanatha, T D Shanafelt, N E Kay, A K Ghosh, The tumor suppressor axis p53/miR-34a regulates Axl expression in B-cell chronic lymphocytic leukemia: implications for therapy in p53-defective CLL patients. Leukemia. ,vol. 28, pp. 451- 455 ,(2014) , 10.1038/LEU.2013.298
L. Bosurgi, J. H. Bernink, V. Delgado Cuevas, N. Gagliani, L. Joannas, E. T. Schmid, C. J. Booth, S. Ghosh, C. V. Rothlin, Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 110, pp. 13091- 13096 ,(2013) , 10.1073/PNAS.1302507110
Thomas Schmidt, Isabel Ben-Batalla, Alexander Schultze, Sonja Loges, Macrophage-tumor crosstalk: role of TAMR tyrosine kinase receptors and of their ligands. Cellular and Molecular Life Sciences. ,vol. 69, pp. 1391- 1414 ,(2012) , 10.1007/S00018-011-0863-7
Mihalis S Kariolis, Yu Rebecca Miao, Douglas S Jones, Shiven Kapur, Irimpan I Mathews, Amato J Giaccia, Jennifer R Cochran, An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis. Nature Chemical Biology. ,vol. 10, pp. 977- 983 ,(2014) , 10.1038/NCHEMBIO.1636
R M A Linger, R A Cohen, C T Cummings, S Sather, J Migdall-Wilson, D H G Middleton, X Lu, A E Barón, W A Franklin, D T Merrick, P Jedlicka, D DeRyckere, L E Heasley, D K Graham, Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer. Oncogene. ,vol. 32, pp. 3420- 3431 ,(2013) , 10.1038/ONC.2012.355
Asish K. Ghosh, Charla Secreto, Justin Boysen, Traci Sassoon, Tait D. Shanafelt, Debabrata Mukhopadhyay, Neil E. Kay, The novel receptor tyrosine kinase Axl is constitutively active in B-cell chronic lymphocytic leukemia and acts as a docking site of nonreceptor kinases: implications for therapy Blood. ,vol. 117, pp. 1928- 1937 ,(2010) , 10.1182/BLOOD-2010-09-305649
Alan Burnett, Meir Wetzler, Bob Löwenberg, Therapeutic Advances in Acute Myeloid Leukemia Journal of Clinical Oncology. ,vol. 29, pp. 487- 494 ,(2011) , 10.1200/JCO.2010.30.1820
Hartmut Döhner, Elihu H. Estey, Sergio Amadori, Frederick R. Appelbaum, Thomas Büchner, Alan K. Burnett, Hervé Dombret, Pierre Fenaux, David Grimwade, Richard A. Larson, Francesco Lo-Coco, Tomoki Naoe, Dietger Niederwieser, Gert J. Ossenkoppele, Miguel A. Sanz, Jorge Sierra, Martin S. Tallman, Bob Löwenberg, Clara D. Bloomfield, Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. ,vol. 115, pp. 453- 474 ,(2010) , 10.1182/BLOOD-2009-07-235358