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Article

PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells

  • Authors:
    • Ekaterina S. Ivanova
    • Victor V. Tatarskiy
    • Margarita A. Yastrebova
    • Alvina I. Khamidullina
    • Alexei V. Shunaev
    • Anastasia A. Kalinina
    • Alexei A. Zeifman
    • Fedor N. Novikov
    • Yulia V. Dutikova
    • Ghermes G. Chilov
    • Alexander A. Shtil
  • View Affiliations / Copyright

    Affiliations: Blokhin National Medical Center of Oncology, 115478 Moscow, Russia, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia, Moscow State University, 119991 Moscow, Russia, Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, and FusionPharma, 119991 Moscow, Russia, Federal Institute of Industrial Property, 125993 Moscow, Russia
  • Pages: 289-297
    |
    Published online on: May 14, 2019
       https://doi.org/10.3892/ijo.2019.4801
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Abstract

A t(9;22) chromosomal translocation which forms the chimeric tyrosine kinase breakpoint cluster region (BCR)‑Abelson murine leukemia viral oncogene homolog 1 (ABL) is a key mechanism underlying the pathogenesis of chronic myelogenous leukemia (CML). Pharmacological inhibition of BCR‑ABL with imatinib (Gleevec) has been reported as an effective targeted therapy; however, mutations (including the kinase domain of ABL) suppress the efficacy of inhibitors. PF‑114, a derivative of the third generation BCR‑ABL inhibitor ponatinib, demonstrated a high inhibitory activity against wild-type and mutant BCR‑ABL forms, such as the clinically important T315I. Furthermore, PF‑114 exhibited preferential kinase selectivity, safety, notable pharmacokinetic properties and therapeutic efficacy in a murine model. Investigation into the mechanisms of CML cell death revealed an exceptional potency of PF‑114 (at low nanomolar concentrations) for the CML‑derived K562 cell line, whereas leukemia cell lines that lack the chimeric tyrosine kinase were markedly more refractory. The molecular ordering of events mechanistically associated with K562 cell death included the dephosphorylation of CrkL adaptor protein followed by inhibition of ERK1/2 and Akt, G1 arrest, a decrease of phosphorylated Bcl‑2‑associated death promoter, Bcl‑2‑like protein 11, BH3 interacting‑domain death agonist, Bcl‑extra large and Bcl‑2 family apoptosis regulator, and reduced mitochondrial transmembrane potential. Increased Annexin V reactivity, activation of caspases and poly(ADP‑ribose)polymerase cleavage were proposed to lead to internucleosomal DNA fragmentation. Thus, PF‑114 may be a potent inducer of apoptosis in CML cells. Nevertheless, activation of STAT3 phosphorylation in response to PF‑114 may permit cell rescue; thus, a combination of BCR‑ABL and STAT3 inhibitors should be considered for improved therapeutic outcome. Collectively, the targeted killing of BCR‑ABL‑positive cells, along with other beneficial properties, such as in vivo characteristics, suggests PF‑114 as a potential candidate for analysis in clinical trials with CML patients.
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View References

1 

Pasternak G, Hochhaus A, Schultheis B and Hehlmann R: Chronic myelogenous leukemia: Molecular and cellular aspects. J Cancer Res Clin Oncol. 124:643–660. 1998. View Article : Google Scholar

2 

Lin X, Qureshi MZ, Attar R, Khalid S, Tahir F, Yaqub A, Aslam A, Yaylim I, De Carlos Back LK, Farooqi AA, et al: Targeting of BCR-ABL: Lessons learned from BCR-ABL inhibition. Cell Mol Biol (Noisy-le-grand). 62:129–137. 2016.

3 

Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, Baccarani M, Deininger MW, Cervantes F, Fujihara S, et al: IRIS Investigators: Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 376:917–927. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, et al: Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 367:2075–2088. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, et al: PACE Investigators: A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 369:1783–1796. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Hoy SM: Ponatinib: A review of its use in adults with chronic myeloid leukaemia or Philadelphia chromosome-positive acute lymphoblastic leukaemia. Drugs. 74:793–806. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Moslehi JJ and Deininger M: Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia. J Clin Oncol. 33:4210–4218. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Mian AA, Rafiei A, Haberbosch I, Zeifman A, Titov I, Stroylov V, Metodieva A, Stroganov O, Novikov F, Brill B, et al: PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation. Leukemia. 29:1104–1114. 2015. View Article : Google Scholar

9 

Chilov GG and Titov IY: Protein kinase inhibitor (versions), use thereof for treating oncological diseases and based pharmaceutical composition. Patent RU2477723 (C2). Filed July 10, 2017; issued August 31, 2017.

10 

Cellosaurus - a knowledge resource on cell lines. Version 29. https://web.expasy.org/cellosaurus/CVCL_0002.

11 

Liu D: The adaptor protein Crk in immune response. Immunol Cell Biol. 92:80–89. 2014. View Article : Google Scholar :

12 

Shchekotikhin AE, Dezhenkova LG, Tsvetkov VB, Luzikov YN, Volodina YL, Tatarskiy VV Jr, Kalinina AA, Treshalin MI, Treshalina HM, Romanenko VI, et al: Discovery of antitumor anthra[2,3-b]furan-3-carboxamides: Optimization of synthesis and evaluation of antitumor properties. Eur J Med Chem. 112:114–129. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Rahbar Saadat Y, Saeidi N, Zununi Vahed S, Barzegari A and Barar J: An update to DNA ladder assay for apoptosis detection. Bioimpacts. 5:25–28. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Rossari F, Minutolo F and Orciuolo E: Past, present, and future of Bcr-Abl inhibitors: From chemical development to clinical efficacy. J Hematol Oncol. 11:842018. View Article : Google Scholar : PubMed/NCBI

15 

Haguet H, Douxfils J, Mullier F, Chatelain C, Graux C and Dogné JM: Risk of arterial and venous occlusive events in chronic myeloid leukemia patients treated with new generation BCR-ABL tyrosine kinase inhibitors: A systematic review and meta-analysis. Expert Opin Drug Saf. 16:5–12. 2017. View Article : Google Scholar

16 

Wehrle J and von Bubnoff N: Ponatinib: A third-generation inhibitor for the treatment of CML. Recent Results Cancer Res. 212:109–118. 2018. View Article : Google Scholar : PubMed/NCBI

17 

Zulbaran-Rojas A, Lin HK, Shi Q, Williams LA, George B, Garcia-Manero G, Jabbour E, O'Brien S, Ravandi F, Wierda W, et al: A prospective analysis of symptom burden for patients with chronic myeloid leukemia in chronic phase treated with frontline second- and third-generation tyrosine kinase inhibitors. Cancer Med. 7:5457–5469. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Aspinall-O'Dea M, Pierce A, Pellicano F, Williamson AJ, Scott MT, Walker MJ, Holyoake TL and Whetton AD: Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines. Nat Protoc. 10:149–168. 2015. View Article : Google Scholar

19 

Lux MP, Fasching PA, Schrauder MG, Hein A, Jud SM, Rauh C and Beckmann MW: The PI3K pathway: Background and treatment approaches. Breast Care (Basel). 11:398–404. 2016. View Article : Google Scholar

20 

Dey N, De P and Leyland-Jones B: PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trials. Pharmacol Ther. 175:91–106. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Nussinov R, Tsai CJ and Jang H: A new view of pathway-driven drug resistance in tumor proliferation. Trends Pharmacol Sci. 38:427–437. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Correia C, Lee SH, Meng XW, Vincelette ND, Knorr KL, Ding H, Nowakowski GS, Dai H and Kaufmann SH: Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment. Biochim Biophys Acta. 1853:1658–1671. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Schutters K and Reutelingsperger C: Phosphatidylserine targeting for diagnosis and treatment of human diseases. Apoptosis. 15:1072–1082. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Chaitanya GV, Steven AJ and Babu PP: PARP-1 cleavage fragments: Signatures of cell-death proteases in neurodegeneration. Cell Commun Signal. 8:312010. View Article : Google Scholar : PubMed/NCBI

25 

Bousoik E and Montazeri Aliabadi H: 'Do We Know Jack' about JAK? A closer look at JAK/STAT signaling pathway. Front Oncol. 8:2872018. View Article : Google Scholar

26 

Ma L, Zhu Z, Jiang L, Sun X, Lu X, Zhou M, Qian S and Jianyong L: Matrine suppresses cell growth of human chronic myeloid leukemia cells via its inhibition of the interleukin-6/Janus activated kinase/signal transducer and activator of transcription 3 signaling cohort. Leuk Lymphoma. 56:2923–2930. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Ma L, Xu Z, Wang J, Zhu Z, Lin G, Jiang L, Lu X and Zou C: Matrine inhibits BCR/ABL mediated ERK/MAPK pathway in human leukemia cells. Oncotarget. 8:108880–108889. 2017. View Article : Google Scholar

28 

Liu C, Nie D, Li J, Du X, Lu Y, Li Y, Zhou J, Jin Y and Pan J: Antitumor effects of blocking protein neddylation in T315I-BCR-ABL leukemia cells and leukemia stem cells. Cancer Res. 78:1522–1536. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Gu Y, Zheng W, Zhang J, Gan X, Ma X, Meng Z, Chen T, Lu X, Wu Z, Huang W, et al: Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis. Leukemia. 30:1282–1289. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Lee HJ, Zhuang G, Cao Y, Du P, Kim HJ and Settleman J: Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells. Cancer Cell. 26:207–221. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Mencalha AL, Corrêa S, Salles D, Du Rocher B, Santiago MF and Abdelhay E: Inhibition of STAT3-interacting protein 1 (STATIP1) promotes STAT3 transcriptional up-regulation and imatinib mesylate resistance in the chronic myeloid leukemia. BMC Cancer. 14:8662014. View Article : Google Scholar : PubMed/NCBI

32 

Wang H, Xie B, Kong Y, Tao Y, Yang G, Gao M, Xu H, Zhan F, Shi J, Zhang Y, et al: Overexpression of RPS27a contributes to enhanced chemoresistance of CML cells to imatinib by the transactivated STAT3. Oncotarget. 7:18638–18650. 2016.PubMed/NCBI

33 

Shi Y, Zhang Z, Qu X, Zhu X, Zhao L, Wei R, Guo Q, Sun L, Yin X, Zhang Y, et al: Roles of STAT3 in leukemia (Review). Int J Oncol. 53:7–20. 2018.PubMed/NCBI

34 

Guanizo AC, Fernando CD, Garama DJ and Gough DJ: STAT3: A multifaceted oncoprotein. Growth Factors. 36:1–14. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Sgrignani J, Garofalo M, Matkovic M, Merulla J, Catapano CV and Cavalli A: Structural biology of STAT3 and its implications for anticancer therapies development. Int J Mol Sci. 19:E15912018. View Article : Google Scholar : PubMed/NCBI

36 

Al-Jamal HA, Jusoh SA, Yong AC, Asan JM, Hassan R and Johan MF: Silencing of suppressor of cytokine signaling-3 due to methylation results in phosphorylation of STAT3 in imatinib resistant BCR-ABL positive chronic myeloid leukemia cells. Asian Pac J Cancer Prev. 15:4555–4561. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Eiring AM, Page BDG, Kraft IL, Mason CC, Vellore NA, Resetca D, Zabriskie MS, Zhang TY, Khorashad JS, Engar AJ, et al: Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy-resistant chronic myeloid leukemia. Leukemia. 31:1253–1254. 2017. View Article : Google Scholar : PubMed/NCBI

38 

Sweet K, Hazlehurst L, Sahakian E, Powers J, Nodzon L, Kayali F, Hyland K, Nelson A and Pinilla-Ibarz J: A phase I clinical trial of ruxolitinib in combination with nilotinib in chronic myeloid leukemia patients with molecular evidence of disease. Leuk Res. 74:89–96. 2018. View Article : Google Scholar : PubMed/NCBI

39 

Singh H, Williams RT and Guy KR: Methods and compositions for the treatment of Bcr-Abl positive lymphoblastic leukemias. Patent US20150133462 A1. Filed May 23, 2013; issued May 14, 2015.

40 

Sahu N, Chan E, Chu F, Pham T, Koeppen H, Forrest W, Merchant M and Settleman J: Cotargeting of MEK and PDGFR/STAT3 pathways to treat pancreatic ductal adenocarcinoma. Mol Cancer Ther. 16:1729–1738. 2017. View Article : Google Scholar : PubMed/NCBI

41 

Ouédraogo ZG, Müller-Barthélémy M, Kemeny JL, Dedieu V, Biau J, Khalil T, Raoelfils LI, Granzotto A, Pereira B, Beaudoin C, et al: STAT3 serine 727 phosphorylation: A relevant target to radiosen-sitize human glioblastoma. Brain Pathol. 26:18–30. 2016. View Article : Google Scholar

42 

Zhou Q, Chen Y, Chen X, Zhao W, Zhong Y, Wang R, Jin M, Qiu Y and Kong D: In vitro antileukemia activity of ZSTK474 on K562 and multidrug resistant K562/A02 cells. Int J Biol Sci. 12:631–638. 2016. View Article : Google Scholar : PubMed/NCBI

43 

Haberbosch I, Rafiei A, Oancea C, Ottmann GO, Ruthardt M and Mian AA: BCR: A new target in resistance mediated by BCR/ABL-315I? Genes Cancer. 7:36–46. 2016.PubMed/NCBI

44 

Mian AA, Schüll M, Zhao Z, Oancea C, Hundertmark A, Beissert T, Ottmann OG and Ruthardt M: The gatekeeper mutation T315I confers resistance against small molecules by increasing or restoring the ABL-kinase activity accompanied by aberrant transphosphorylation of endogenous BCR, even in loss-of-function mutants of BCR/ABL. Leukemia. 23:1614–1621. 2009. View Article : Google Scholar : PubMed/NCBI

45 

NIH: U.S. National Library of Medicine. ClinicalTrials. Study to evaluate tolerability, safety, pharmacokinetics and preliminary efficacy of PF-114 for oral administration in adults with Ph+ chronic myeloid leukemia, which is resistant to the 2-nd generation Bcr-Abl inhibitors or Has T315I mutation in the BCR-ABL gene. (NCT02885766). https://clinicaltrials.gov/ct2/show/NCT02885766.

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Copy and paste a formatted citation
Spandidos Publications style
Ivanova ES, Tatarskiy VV, Yastrebova MA, Khamidullina AI, Shunaev AV, Kalinina AA, Zeifman AA, Novikov FN, Dutikova YV, Chilov GG, Chilov GG, et al: PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells. Int J Oncol 55: 289-297, 2019.
APA
Ivanova, E.S., Tatarskiy, V.V., Yastrebova, M.A., Khamidullina, A.I., Shunaev, A.V., Kalinina, A.A. ... Shtil, A.A. (2019). PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells. International Journal of Oncology, 55, 289-297. https://doi.org/10.3892/ijo.2019.4801
MLA
Ivanova, E. S., Tatarskiy, V. V., Yastrebova, M. A., Khamidullina, A. I., Shunaev, A. V., Kalinina, A. A., Zeifman, A. A., Novikov, F. N., Dutikova, Y. V., Chilov, G. G., Shtil, A. A."PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells". International Journal of Oncology 55.1 (2019): 289-297.
Chicago
Ivanova, E. S., Tatarskiy, V. V., Yastrebova, M. A., Khamidullina, A. I., Shunaev, A. V., Kalinina, A. A., Zeifman, A. A., Novikov, F. N., Dutikova, Y. V., Chilov, G. G., Shtil, A. A."PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells". International Journal of Oncology 55, no. 1 (2019): 289-297. https://doi.org/10.3892/ijo.2019.4801
Copy and paste a formatted citation
x
Spandidos Publications style
Ivanova ES, Tatarskiy VV, Yastrebova MA, Khamidullina AI, Shunaev AV, Kalinina AA, Zeifman AA, Novikov FN, Dutikova YV, Chilov GG, Chilov GG, et al: PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells. Int J Oncol 55: 289-297, 2019.
APA
Ivanova, E.S., Tatarskiy, V.V., Yastrebova, M.A., Khamidullina, A.I., Shunaev, A.V., Kalinina, A.A. ... Shtil, A.A. (2019). PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells. International Journal of Oncology, 55, 289-297. https://doi.org/10.3892/ijo.2019.4801
MLA
Ivanova, E. S., Tatarskiy, V. V., Yastrebova, M. A., Khamidullina, A. I., Shunaev, A. V., Kalinina, A. A., Zeifman, A. A., Novikov, F. N., Dutikova, Y. V., Chilov, G. G., Shtil, A. A."PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells". International Journal of Oncology 55.1 (2019): 289-297.
Chicago
Ivanova, E. S., Tatarskiy, V. V., Yastrebova, M. A., Khamidullina, A. I., Shunaev, A. V., Kalinina, A. A., Zeifman, A. A., Novikov, F. N., Dutikova, Y. V., Chilov, G. G., Shtil, A. A."PF‑114, a novel selective inhibitor of BCR‑ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells". International Journal of Oncology 55, no. 1 (2019): 289-297. https://doi.org/10.3892/ijo.2019.4801
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