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Critical Reviews™ in Oncogenesis

Published 4 issues per year

ISSN Print: 0893-9675

ISSN Online: 2162-6448

SJR: 0.395 SNIP: 0.322 CiteScore™:: 2.5 H-Index: 54

Indexed in

TAM Receptors in Leukemia: Expression, Signaling, and Therapeutic Implications

Volume 16, Issue 1-2, 2011, pp. 47-63
DOI: 10.1615/CritRevOncog.v16.i1-2.60
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ABSTRACT

In the past 30 years there has been remarkable progress in the treatment of leukemia and lymphoma. However, current treatments are largely ineffective against relapsed leukemia and, in the case of pediatric patients, are often associated with severe long-term toxicities. Thus, there continues to be a critical need for the development of effective biologically targeted therapies. The TAM family of receptor tyrosine kinases−Tyro3, Axl, and Mer−plays an important role in normal hematopoiesis, including natural killer cell maturation, macrophage function, and platelet activation and signaling. Furthermore, TAM receptor activation leads to upregulation of pro-survival and proliferation signaling pathways, and aberrant TAM receptor expression contributes to cancer development, including myeloid and lymphoid leukemia. This review summarizes the role of TAM receptors in leukemia. We outline TAM receptor expression patterns in different forms of leukemia, describe potential mechanisms leading to their overexpression, and delineate the signaling pathways downstream of receptor activation that have been implicated in leukemogenesis. Finally, we discuss the current research focused on inhibitors against these receptors in an effort to develop new therapeutic strategies for leukemia.

CITED BY
  1. 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, Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma, Blood, 122, 14, 2013. Crossref

  2. Liu Jing, Zhang Weihe, Stashko Michael A., DeRyckere Deborah, Cummings Christopher T., Hunter Debra, Yang Chao, Jayakody Chatura N., Cheng Nancy, Simpson Catherine, Norris-Drouin Jacqueline, Sather Susan, Kireev Dmitri, Janzen William P., Earp H. Shelton, Graham Douglas K., Frye Stephen V., Wang Xiaodong, UNC1062, a new and potent Mer inhibitor, European Journal of Medicinal Chemistry, 65, 2013. Crossref

  3. Brandao L N, Winges A, Christoph S, Sather S, Migdall-Wilson J, Schlegel J, McGranahan A, Gao D, Liang X, DeRyckere D, Graham D K, Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia, Blood Cancer Journal, 3, 1, 2013. Crossref

  4. Suleiman Lutfi, Négrier Claude, Boukerche Habib, Protein S: A multifunctional anticoagulant vitamin K-dependent protein at the crossroads of coagulation, inflammation, angiogenesis, and cancer, Critical Reviews in Oncology/Hematology, 88, 3, 2013. Crossref

  5. Xu Fei, Li Hongling, Sun Yong, Inhibition of Axl improves the targeted therapy against ALK-mutated neuroblastoma, Biochemical and Biophysical Research Communications, 454, 4, 2014. Crossref

  6. Wang Xiaodong, Frye Stephen, , 49, 2014. Crossref

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  8. Balupuri Anand, Balasubramanian Pavithra K., Cho Seung Joo, Molecular modeling study on Mer kinase inhibitors using 3D-QSAR and docking approaches, Medicinal Chemistry Research, 24, 10, 2015. Crossref

  9. Balupuri Anand, Balasubramanian Pavithra K., Cho Seung Joo, Determination of structural requirements of Mer kinase inhibitors and binding interaction analysis using in silico approaches, Medicinal Chemistry Research, 25, 12, 2016. Crossref

  10. Migdall-Wilson Justine, Bates Christine, Schlegel Jennifer, Brandão Luis, Linger Rachel M. A., DeRyckere Deborah, Graham Douglas K., Agoulnik Irina, Prolonged Exposure to a Mer Ligand in Leukemia: Gas6 Favors Expression of a Partial Mer Glycoform and Reveals a Novel Role for Mer in the Nucleus, PLoS ONE, 7, 2, 2012. Crossref

  11. Huey Madeline, Minson Katherine, Earp H., DeRyckere Deborah, Graham Douglas, Targeting the TAM Receptors in Leukemia, Cancers, 8, 11, 2016. Crossref

  12. Bi Shaojie, Wang Chunyan, Li Yixin, Zhang Wei, Zhang Juan, Lv Zhaopeng, Wang Junxia, LncRNA-MALAT1-mediated Axl promotes cell invasion and migration in human neuroblastoma, Tumor Biology, 39, 5, 2017. Crossref

  13. Uribe Diana J., Mandell Edward K., Watson Adam, Martinez Jesse D., Leighton Jonathan A., Ghosh Sourav, Rothlin Carla V., Castresana Javier S, The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer, PLOS ONE, 12, 7, 2017. Crossref

  14. Carter Jenna L., Hege Katie, Yang Jay, Kalpage Hasini A., Su Yongwei, Edwards Holly, Hüttemann Maik, Taub Jeffrey W., Ge Yubin, Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy, Signal Transduction and Targeted Therapy, 5, 1, 2020. Crossref

  15. Zhang Guoan , Wang Meng , Zhao Hongli , Cui Wen , Function of Axl receptor tyrosine kinase in non-small cell lung cancer (Review), Oncology Letters, 2017. Crossref

  16. Zhang Weihe, Zhang Dehui, Stashko Michael A., DeRyckere Deborah, Hunter Debra, Kireev Dmitri, Miley Michael J., Cummings Christopher, Lee Minjung, Norris-Drouin Jacqueline, Stewart Wendy M., Sather Susan, Zhou Yingqiu, Kirkpatrick Gregory, Machius Mischa, Janzen William P., Earp H. Shelton, Graham Douglas K., Frye Stephen V., Wang Xiaodong, Pseudo-Cyclization through Intramolecular Hydrogen Bond Enables Discovery of Pyridine Substituted Pyrimidines as New Mer Kinase Inhibitors, Journal of Medicinal Chemistry, 56, 23, 2013. Crossref

  17. Christoph Sandra, DeRyckere Deborah, Schlegel Jennifer, Frazer J. Kimble, Batchelor Lance A., Trakhimets Alesia Y., Sather Susan, Hunter Debra M., Cummings Christopher T., Liu Jing, Yang Chao, Kireev Dmitri, Simpson Catherine, Norris-Drouin Jacqueline, Hull-Ryde Emily A., Janzen William P., Johnson Gary L., Wang Xiaodong, Frye Stephen V., Earp H. Shelton, Graham Douglas K., UNC569, a Novel Small-Molecule Mer Inhibitor with Efficacy against Acute Lymphoblastic Leukemia In Vitro and In Vivo , Molecular Cancer Therapeutics, 12, 11, 2013. Crossref

  18. Whitman S P, Kohlschmidt J, Maharry K, Volinia S, Mrózek K, Nicolet D, Schwind S, Becker H, Metzeler K H, Mendler J H, Eisfeld A-K, Carroll A J, Powell B L, Carter T H, Baer M R, Kolitz J E, Park I-K, Stone R M, Caligiuri M A, Marcucci G, Bloomfield C D, GAS6 expression identifies high-risk adult AML patients: potential implications for therapy, Leukemia, 28, 6, 2014. Crossref

  19. Linger R M A, Cohen R A, Cummings C T, Sather S, Migdall-Wilson J, Middleton D H G, Lu X, Barón A E, Franklin W A, Merrick D T, Jedlicka P, DeRyckere D, Heasley L E, Graham D K, Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer, Oncogene, 32, 29, 2013. Crossref

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