The Role of STAT5 in Tyrosine Kinase Inhibitor (IMATINIB) Resistance in CML Patients

Authors

  • Anastasia Putri Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • Ikhwan Rinaldi Division of Haematology and Medical Oncology. Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia
  • Melva Louisa Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta , Indonesia
  • Soekamto Koesnoe Division of Allergy and Clinical Immunology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia

Keywords:

chronic Myeloid Leukemia, STAT5, Imatinib, tyrosine kinase inhibitor, resistance

Abstract

Chronic myeloid leukemia (CML) is a clonal haemopoietic stem cell disorders with reciprocal translocation in chromosome 9 (ch9) and 22 (ch22) which cause the fusion of Break cluster region-Abelson murine leukemia (BCR-ABL) oncogene. This fusion will activate tyrosine kinase. Imatinib mesylate is the first tyrosine kinase inhibitor (TKI), which could change the prognosis of CML patients. However, there is a resistance to TKI’s, and based on transcriptomic study, increase expression of gen signal transducer and activator of transcription (STAT) 5A and runt-related transcription factor 3 (RUNX3) can cause resistance to TKI’s. The STAT5 protein, which in normal myeloid cells being activated by cytokine, in CML patients was activated even without cytokines. STAT5 refer to STAT5A and STAT5B, however they have might have different role in hematopoietic stem cells or in CML cells. This review summarizes the role of STAT5 in tyrosine kinase inhibitor resistance in CML patients.

References

Apperley JF. Chronic myeloid leukaemia. Lancet. 2015;385(9976):1447-59

Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. American journal of hematology. 2018;93(3):442-59.

Deininger MW, Vieira S, Mendiola R, Schultheis B, Goldman JM, Melo JV. BCR-ABL tyrosine kinase activity regulates the expression of multiple genes implicated in the pathogenesis of chronic myeloid leukemia. Cancer research. 2000;60(7):2049-55.

Casetti, Luana. New roles of STAT5 factors in chronic myeloid leukemia cell maintenance. PhD diss., Université René Descartes-Paris V, 2013.

National Comprehensive Cancer Network. Chronic Myeloid Leukemia (Version 1.2019). https://www.nccn.org/professionals/physician_gls/PDF/cml.pdf. Accessed Nov 30, 2018.

Wei G, Rafiyath S, Liu D. First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib. J Hematol Oncol. 2010;3(1):47.

Zhang WW, Cortes JE, Yao H, et al. Predictors of primary imatinib resistance in chronic myelogenous leukemia are distinct from those in secondary imatinib resistance. J Clin Oncol. 2009;27(22):3642.

Bhamidipati PK, Kantarjian H, Cortes J, Cornelison AM, Jabbour E. Management of imatinib-resistant patients with chronic myeloid leukemia. Ther Adv Hematol. 2013;4(2):103-17.

Mohr A, Chatain N, Domoszlai T, et al. Dynamics and non-canonical aspects of JAK/STAT signalling. Europ J Cell Biol. 2012;91(6-7):524-32.

Mi T, Wang Z, Bunting K. The cooperative relationship between STAT5 and reactive oxygen species in leukemia: Mechanism and therapeutic potential. Cancers. 2018;10(10):359.

Ilaria RL, Van Etten RA. P210 and P190BCR/ABL induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J Biol Chemistry. 1996;271(49):31704-10.

Gouilleux F, Wakao H, Mundt M, Groner B. Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. The EMBO J. 1994;13(18):4361-9.

Warsch W, Grundschober E, Sexl V. Adding a new facet to STAT5 in CML: multitasking for leukemic cells. Cell cycle (Georgetown, Tex.). 2013;12(12):1813-4.

Constantinescu S.N., Girardot M., Pecquet C. Mining for JAK-STAT mutations in cancer. Trends Biochem. Sci. 2008;33:122–31.

Silva C.M. Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene. 2004;23:8017–23.

Ozawa Y, Williams AH, Estes ML, Matsushita N, Boschelli F, Jove R, List AF. Src family kinases promote AML cell survival through activation of signal transducers and activators of transcription (STAT) Leuk Res. 2008;32:893–903.

Bourgeais J, Gouilleux-Gruart V, Gouilleux F. Oxidative metabolism in cancer: A STAT affair? JAKSTAT. 2013;2:e25764.

Warsch W, Grundschober E, Berger A, Gille L, Cerny-Reiterer S, Tigan AS, Hoelbl-Kovacic A, Valent P, Moriggl R, Sexl V. STAT5 triggers BCR-ABL1 mutation by mediating ROS production in chronic myeloid leukaemia. Oncotarget. 2012;3:1669–87.

Casetti L, Martin-Lanneree S, Najjar I, Plo I, Auge S, Roy L, Chomel JC, Lauret E, Turhan AG, Dusanter-Fourt I. Differential contributions of STAT5a and STAT5b to stress protection and tyrosine kinase inhibitor resistance of chronic myeloid leukemia stem/progenitor cells. Cancer Res. 2013;73:2052–8.

Schaller-Schönitz M, Barzan D, Williamson AJ, Griffiths JR, Dallmann I, Battmer K, Ganser A, Whetton AD, Scherr M, Eder M. BCR-ABL Affects STAT5A and STAT5B Differentially. PloS one. 2014;9(5):e97243.

Chatain N, Ziegler P, Fahrenkamp D, et al. Src family kinases mediate cytoplasmic retention of activated STAT5 in BCR–ABL-positive cells. Oncogene. 2013;32(31):3587.

Furqan M, Akinleye A, Mukhi N, Mittal V, Chen Y, et al. (2013) STAT inhibitors for cancer therapy. J Hematol Oncol. 2006;90(8722):6-90.

Nelson EA, Walker SR, Weisberg E, et al. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood. 2011;117(12):3421-9.

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Published

2020-02-10

How to Cite

Putri, A., Rinaldi, I., Louisa, M., & Koesnoe, S. (2020). The Role of STAT5 in Tyrosine Kinase Inhibitor (IMATINIB) Resistance in CML Patients. Acta Medica Indonesiana, 51(4), 348. Retrieved from http://www.actamedindones.org/index.php/ijim/article/view/978

Issue

Vol. 51 No. 4 (2019): Acta Medica Indonesiana

Section

REVIEW ARTICLE

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