摘要
Future Medicinal ChemistryVol. 12, No. 23 EditorialNovel strategies to eradicate resistant cells in chronic myeloid leukemiaAnna M Schoepf & Ronald GustAnna M Schoepf https://orcid.org/0000-0002-7536-1906Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI – Center for Molecular Biosciences Innsbruck, University of Innsbruck, CCB – Centrum for Chemistry & Biomedicine, Innrain 80–82, 6020 Innsbruck, Austria & Ronald Gust *Author for correspondence: E-mail Address: ronald.gust@uibk.ac.athttps://orcid.org/0000-0002-0427-4012Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI – Center for Molecular Biosciences Innsbruck, University of Innsbruck, CCB – Centrum for Chemistry & Biomedicine, Innrain 80–82, 6020 Innsbruck, AustriaPublished Online:24 Nov 2020https://doi.org/10.4155/fmc-2020-0278AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: cancer stem cells (CSCs)cell death modulatorschronic myeloid leukemia (CML)sensitizerstherapy resistancetyrosine kinase inhibitor (TKI)References1. Hehlmann R, Hochhaus A, Baccarani M. Chronic myeloid leukaemia. Lancet 370(9584), 342–350 (2007).Crossref, Medline, CAS, Google Scholar2. Saussele S, Richter J, Hochhaus A, Mahon FX. The concept of treatment-free remission in chronic myeloid leukemia. Leukemia 30(8), 1638–1647 (2016).Crossref, Medline, CAS, Google Scholar3. Yaghmaie M, Yeung CCS. Molecular mechanisms of resistance to tyrosine kinase inhibitors. Curr. Hematol. Malig. Rep. 14(5), 395–404 (2019).Crossref, Medline, Google Scholar4. Patel AB, O'Hare T, Deininger MW. Mechanisms of resistance to ABL kinase inhibition in chronic myeloid leukemia and the development of next generation ABL kinase inhibitors. Hematol. Oncol. Clin. North Am. 31(4), 589–612 (2017).Crossref, Medline, Google Scholar5. Eadie LN, Saunders VA, Branford S, White DL, Hughes TP. The new allosteric inhibitor asciminib is susceptible to resistance mediated by ABCB1 and ABCG2 overexpression in vitro. Oncotarget 9(17), 13423–13437 (2018).Crossref, Medline, Google Scholar6. Borthakur G, Dombret H, Schafhausen P et al. A Phase I study of danusertib (PHA-739358) in adult patients with accelerated or blastic phase chronic myeloid leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib and/or other second generation c-ABL therapy. Haematologica 100(7), 898–904 (2015).Medline, CAS, Google Scholar7. Rumjanek VM, Vidal RS, Maia RC. Multidrug resistance in chronic myeloid leukaemia: how much can we learn from MDR–CML cell lines? Biosci. Rep. 33(6), 875–888 (2013).Crossref, CAS, Google Scholar8. Loscocco F, Visani G, Galimberti S, Curti A, Isidori A. BCR-ABL independent mechanisms of resistance in chronic myeloid leukemia. Front. Oncol. 9, 939–939 (2019).Crossref, Medline, Google Scholar9. Jiang X, Zhao Y, Smith C et al. Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies. Leukemia 21, 926–935 (2007).Crossref, Medline, CAS, Google Scholar10. Winer ES, DeAngelo DJ. A review of omacetaxine: a chronic myeloid leukemia treatment resurrected. Oncol. Ther. 6(1), 9–20 (2018).Crossref, Medline, Google Scholar11. Mitchell R, Hopcroft LEM, Baquero P et al. Targeting BCR-ABL-independent TKI resistance in chronic myeloid leukemia by mTOR and autophagy inhibition. J. Natl. Cancer Inst. 110(5), 467–478 (2017).Crossref, Google Scholar12. Wagle M, Eiring AM, Wongchenko M et al. A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Leukemia 30(7), 1493–1501 (2016).Crossref, Medline, CAS, Google Scholar13. Prost S, Relouzat F, Spentchian M et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature 525(7569), 380–383 (2015).Crossref, Medline, CAS, Google Scholar14. Schoepf AM, Salcher S, Obexer P, Gust R. Overcoming imatinib resistance in chronic myelogenous leukemia cells using noncytotoxic cell death modulators. Eur. J. Med. Chem. 185, 111748 (2020).Crossref, Medline, CAS, Google Scholar15. Schoepf AM, Salcher S, Obexer P, Gust R. Identification and development of noncytotoxic cell death modulators: impact of sartans and derivatives on PPARγ activation and on growth of imatinib-resistant chronic myelogenous leukemia cells. Eur. J. Med. Chem. 195, 112258 (2020).Crossref, Medline, CAS, Google Scholar16. Lopes ABP, Miranda EC, Póvoa VMO et al. Pioglitazone did not affect PPAR-γ, STAT5, HIF2α and CITED2 gene expression in chronic myeloid leukemia patients with deep molecular response. Blood 134, 1637–1637 (2019).Crossref, Google Scholar17. Hadzijusufovic E, Keller A, Berger D et al. STAT5 is expressed in CD34(+)/CD38(−) stem cells and serves as a potential molecular target in Ph-negative myeloproliferative neoplasms. Cancers (Basel) 12(4), 1021 (2020).Crossref, CAS, Google Scholar18. Wang L, Giannoudis A, Austin G, Clark RE. Peroxisome proliferator-activated receptor activation increases imatinib uptake and killing of chronic myeloid leukemia cells. Exp. Hematol. 40(10), 811–819 (2012).Crossref, Medline, Google Scholar19. Wang J, Lu L, Kok CH et al. Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells. Haematologica 102(5), 843–853 (2017).Crossref, Medline, CAS, Google Scholar20. Choi YH, Yu AM. ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr. Pharm. Des. 20(5), 793–807 (2014).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetails Vol. 12, No. 23 Follow us on social media for the latest updates Metrics Downloaded 115 times History Received 22 August 2020 Accepted 3 September 2020 Published online 24 November 2020 Published in print December 2020 Information© 2020 Newlands PressKeywordscancer stem cells (CSCs)cell death modulatorschronic myeloid leukemia (CML)sensitizerstherapy resistancetyrosine kinase inhibitor (TKI)Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download