Imipramine blue sensitively and selectively targets FLT3-ITD positive acute myeloid leukemia cells

Scientific Reports

Volumn 7, Issue 1, 2017, Pages

  Metts, Jonathan ^a,b   Bradley, Heath L ^a,b   Wang, Zhengqi ^a,b   Shah, Neil P ^c   Kapur, Reuben ^d   Arbiser, Jack L ^a,e   Bunting, Kevin D ^a,b  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CHILDREN'S HEALTHCARE OF ATLANTA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d INDIANA UNIVERSITY   (United States)

^e ATLANTA VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CALCIUM; CD135 ANTIGEN; FLT3 PROTEIN, HUMAN; IMIPRAMINE; REACTIVE OXYGEN METABOLITE; STAT5 PROTEIN;

ACUTE MYELOID LEUKEMIA; APOPTOSIS; CYTOSOL; DRUG EFFECT; GENE DUPLICATION; GENETICS; HUMAN; LYSOSOME; METABOLISM; MITOCHONDRION; TANDEM REPEAT; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CALCIUM; CELL LINE, TUMOR; CYTOSOL; FMS-LIKE TYROSINE KINASE 3; GENE DUPLICATION; HUMANS; IMIPRAMINE; LEUKEMIA, MYELOID, ACUTE; LYSOSOMES; MITOCHONDRIA; REACTIVE OXYGEN SPECIES; STAT5 TRANSCRIPTION FACTOR; TANDEM REPEAT SEQUENCES;

EID: 85021636928     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-017-04796-1     Document Type: Article

References (47)

1. Small, D. Targeting FLT3 for the treatment of leukemia. Semin Hematol 45, S17-21, doi:10.1053/j.seminhematol.2008.07.007 (2008).
2. Konig, H., Levis, M. Targeting FLT3 to treat leukemia. Expert opinion on therapeutic targets 19, 37-54, doi:10.1517/14728222.201 4.960843 (2015).
3. Kayser, S., Levis, M. J. FLT3 tyrosine kinase inhibitors in acute myeloid leukemia: Clinical implications and limitations. Leuk Lymphoma 55, 243-255, doi:10.3109/10428194.2013.800198 (2014).
4. Choudhary, C., et al. Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol.Cell 36, 326-339 (2009).
5. Chan, P. M. Differential signaling of Flt3 activating mutations in acute myeloid leukemia: A working model. Protein & cell 2, 108-115, doi:10.1007/s13238-011-1020-7 (2011).
6. Schmidt-Arras, D., et al. Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality. Blood. 113, 3568-3576 (2009).
7. Sallmyr, A., et al. Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, misrepair: Implications for poor prognosis in AML. Blood 111, 3173-3182 (2008).
8. Jayavelu, A. K., et al. NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells. Leukemia 30, 473-483, doi:10.1038/leu.2015.234 (2016).
9. Woolley, J. F., et al. H2O2 production downstream of FLT3 is mediated by p22phox in the endoplasmic reticulum and is required for STAT5 signalling. PLoS.ONE. 7, e34050 (2012).
10. Munson, J. M., et al. Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma. Sci. Transl.Med. 4, 127ra136 (2012).
11. Laidlaw, K. M., et al. Cooperation of imipramine blue and tyrosine kinase blockade demonstrates activity against chronic myeloid leukemia. Oncotarget, doi:10.18632/oncotarget.10541 (2016).
12. Rajamanickam, S., et al. Inhibition of FoxM1-Mediated DNA Repair by Imipramine Blue Suppresses Breast Cancer Growth and Metastasis. Clin Cancer Res 22, 3524-3536, doi:10.1158/1078-0432.ccr-15-2535 (2016).
13. Yang, W. H., et al. Imipramine blue halts head and neck cancer invasion through promoting F-box and leucine-rich repeat protein 14-mediated Twist1 degradation. Oncogene 35, 2287-2298, doi:10.1038/onc.2015.291 (2016).
14. Klingenberg, M., Becker, J., Eberth, S., Kube, D., Wilting, J. The NADPH oxidase inhibitor imipramine-blue in the treatment of Burkitt lymphoma. Molecular cancer therapeutics 13, 833-841, doi:10.1158/1535-7163.mct-13-0688 (2014).
15. Garattini, E., et al. ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: Modulation of intracellular calcium homeostasis. Blood 103, 194-207, doi:10.1182/blood-2003-05-1577 (2004).
16. Angka, L., et al. Glucopsychosine increases cytosolic calcium to induce calpain-mediated apoptosis of acute myeloid leukemia cells. Cancer letters 348, 29-37, doi:10.1016/j.canlet.2014.03.003 (2014).
17. Smith, C. C., et al. Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD. Blood. 121, 3165-3171 (2013).
18. Boitano, A. E., et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science. 329, 1345-1348 (2010).
19. Pabst, C., et al. Identification of small molecules that support human leukemia stem cell activity ex vivo. Nat.Methods. 11, 436-442 (2014).
20. Perelman, A., et al. JC-1: Alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell death & disease 3, e430, doi:10.1038/cddis.2012.171 (2012).
21. Li, G., et al. Effective targeting of STAT5-mediated survival in myeloproliferative neoplasms using ABT-737 combined with rapamycin. Leukemia. 24, 1397-1405 (2010).
22. Nelson, E. A., et al. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood 117, 3421-3429, doi:10.1182/blood-2009-11-255232 (2011).
23. Nelson, E. A., et al. The STAT5 Inhibitor Pimozide Displays Efficacy in Models of Acute Myelogenous Leukemia Driven by FLT3 Mutations. Genes & cancer 3, 503-511, doi:10.1177/1947601912466555 (2012).
24. Kazmi, F., et al. Lysosomal sequestration (trapping) of lipophilic amine (cationic amphiphilic) drugs in immortalized human hepatocytes (Fa2N-4 cells). Drug metabolism and disposition: The biological fate of chemicals 41, 897-905, doi:10.1124/dmd.112.050054 (2013).
25. Smith, C. C., et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 485, 260-263, doi:10.1038/nature11016 (2012).
26. Lee, B. H., et al. FLT3 internal tandem duplication mutations induce myeloproliferative or lymphoid disease in a transgenic mouse model. Oncogene 24, 7882-7892 (2005).
27. Man, C. H., et al. Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: Favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood 119, 5133-5143, doi:10.1182/blood-2011-06-363960 (2012).
28. Leung, A. Y., Man, C. H., Kwong, Y. L. FLT3 inhibition: A moving and evolving target in acute myeloid leukaemia. Leukemia 27, 260-268, doi:10.1038/leu.2012.195 (2013).
29. Giorgi, C., et al. Mitochondrial Ca(2+) and apoptosis. Cell calcium 52, 36-43, doi:10.1016/j.ceca.2012.02.008 (2012).
30. Bygrave, F. L., Benedetti, A. What is the concentration of calcium ions in the endoplasmic reticulum Cell calcium 19, 547-551 (1996).
31. Lloyd-Evans, E., et al. Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14, 1247-1255, doi:10.1038/nm.1876 (2008).
32. Choudhary, C., et al. Activation mechanisms of STAT5 by oncogenic Flt3-ITD. Blood. 110, 370-374 (2007).
33. Benekli, M., Baer, M. R., Baumann, H., Wetzler, M. Signal transducer and activator of transcription proteins in leukemias. Blood 101, 2940-2954 (2003).
34. Bunting, K. D. STAT5 signaling in normal and pathologic hematopoiesis. Front Biosci. 12, 2807-2820 (2007).
35. Lai, P. S., et al. A STAT inhibitor patent review: Progress since 2011. Expert opinion on therapeutic patents 25, 1397-1421, doi:10.151 7/13543776.2015.1086749 (2015).
36. Cumaraswamy, A. A., et al. Nanomolar-Potency Small Molecule Inhibitor of STAT5 Protein. ACS medicinal chemistry letters 5, 1202-1206, doi:10.1021/ml500165r (2014).
37. Page, B. D., et al. Small molecule STAT5-SH2 domain inhibitors exhibit potent antileukemia activity. Journal of medicinal chemistry 55, 1047-1055, doi:10.1021/jm200720n (2012).
38. Hole, P. S., et al. Overproduction of NOX-derived ROS in AML promotes proliferation and is associated with defective oxidative stress signaling. Blood 122, 3322-3330, doi:10.1182/blood-2013-04-491944 (2013).
39. Rhee, S. G. Cell signaling. H2O2, a necessary evil for cell signaling. Science 312, 1882-1883, doi:10.1126/science.1130481 (2006).
40. Stanicka, J., Russell, E. G., Woolley, J. F., Cotter, T. G. NADPH oxidase-generated hydrogen peroxide induces DNA damage in mutant FLT3-expressing leukemia cells. J Biol Chem 290, 9348-9361, doi:10.1074/jbc.M113.510495 (2015).
41. Russell, E. G., Cotter, T. G. New Insight into the Role of Reactive Oxygen Species (ROS) in Cellular Signal-Transduction Processes. International review of cell and molecular biology 319, 221-254, doi:10.1016/bs.ircmb.2015.07.004 (2015).
42. Morgan, A. J., Platt, F. M., Lloyd-Evans, E., Galione, A. Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. Biochem J 439, 349-374, doi:10.1042/bj20110949 (2011).
43. Raffaello, A., Mammucari, C., Gherardi, G., Rizzuto, R. Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum, Mitochondria, Lysosomes. Trends Biochem Sci, doi:10.1016/j.tibs.2016.09.001 (2016).
44. La Rovere, R. M., Roest, G., Bultynck, G., Parys, J. B. Intracellular Ca(2+) signaling and Ca(2+) microdomains in the control of cell survival, apoptosis and autophagy. Cell calcium 60, 74-87, doi:10.1016/j.ceca.2016.04.005 (2016).
45. Pesakhov, S., et al. Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid. Oncotarget, doi:10.18632/oncotarget.7240 (2016).
46. Zhitomirsky, B., Assaraf, Y. G. Lysosomes as mediators of drug resistance in cancer. Drug resistance updates: Reviews and commentaries in antimicrobial and anticancer chemotherapy 24, 23-33, doi:10.1016/j.drup.2015.11.004 (2016).
47. Denmeade, S. R., Isaacs, J. T. The SERCA pump as a therapeutic target: Making a "smart bomb" for prostate cancer. Cancer biology & therapy 4, 14-22 (2005).