347
Views
19
CrossRef citations to date
0
Altmetric
Review

The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia

, , &
Pages 583-590 | Received 17 Feb 2017, Accepted 19 Apr 2017, Published online: 02 May 2017

References

  • Howlader NNA, Krapcho M, Miller D, et al., editors. SEER cancer statistics review, 1975-2013. National Cancer Institute; 2016 Apr. Available from: http://seer.cancer.gov/csr/1975_2013/.
  • Klepin HD, Balducci L. Acute myelogenous leukemia in older adults. Oncologist. 2009 Mar;14:222–232.
  • Okuyama N, Sperr WR, Kadar K, et al. Prognosis of acute myeloid leukemia transformed from myelodysplastic syndromes: a multicenter retrospective study. Leuk Res. 2013;37:862–867.
  • Leone G, Voso MT, Sica S, et al. Therapy related leukemias: susceptibility, prevention and treatment. Leuk Lymphoma. 2001;41:255–276.
  • Papaemmanuil E, Dohner H, Campbell PJ. Genomic classification in acute myeloid leukemia. N Engl J Med. 2016 Sep;01(375):900–901.
  • Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013 May 30;368:2059–2074.
  • Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2016 Jan 07;127:29–41.
  • Metzeler KH, Herold T, Rothenberg-Thurley M, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016 Aug;04(128):686–698.
  • Hatzimichael E, Georgiou G, Benetatos L, et al. Gene mutations and molecularly targeted therapies in acute myeloid leukemia. Am J Blood Res. 2013;3:29–51.
  • He J, Abdel-Wahab O, Nahas MK, et al. Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting. Blood. 2016 Jun 16;127:3004–3014.
  • Coombs CC, Tallman MS, Levine RL. Molecular therapy for acute myeloid leukaemia. Nat Rev Clin Oncol. 2016 May;13:305–318.
  • Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129:424–447.
  • Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016 Jan 07;127:53–61.
  • Yanada M, Kurosawa S, Kobayashi T, et al. Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for younger patients with acute myeloid leukemia: a registry-based study. Bone Marrow Transplant. 2017 Jan 23;1-7.
  • Weisdorf DJ, Millard HR, Horowitz MM, et al. Allogeneic transplantation for advanced acute myeloid leukemia: the value of complete remission. Cancer. 2017 Jan 24. [Epub ahead of print].
  • Ballen KK. Is there a best graft source of transplantation in acute myeloid leukemia? Best Pract Res Clin Haematol. 2015 Jun-Sep;28:147–154.
  • Khan I, Altman JK, Licht JD. New strategies in acute myeloid leukemia: redefining prognostic markers to guide therapy. Clin Cancer Res. 2012 Oct 01;18:5163–5171.
  • Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012 Mar 22;366:1079–1089.
  • Dawson MA, Kouzarides T, Huntly BJ. Targeting epigenetic readers in cancer. N Engl J Med. 2012 Aug 16;367:647–657.
  • Cashen AF, Schiller GJ, O’Donnell MR, et al. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010 Feb 01;28:556–561.
  • Stein EM, Tallman MS. Emerging therapeutic drugs for AML. Blood. 2016 Jan 07;127:71–78.
  • Ryland LK, Fox TE, Liu X, et al. Dysregulation of sphingolipid metabolism in cancer. Cancer Biol Ther. 2011 Jan 15;11:138–149.
  • Haimovitz-Friedman A, Kolesnick RN, Fuks Z. Ceramide signaling in apoptosis. Br Med Bull. 1997;53:539–553.
  • Spiegel S, Foster D, Kolesnick R. Signal transduction through lipid second messengers. Curr Opin Cell Biol. 1996 Apr;8:159–167.
  • Mao C, Obeid LM. Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate. Biochim Biophys Acta. 2008 Sep;1781:424–434.
  • Morad SA, Cabot MC. Ceramide-orchestrated signalling in cancer cells. Nat Rev Cancer. 2013 Jan;13:51–65.
  • Tan SF, Liu X, Fox TE, et al. Acid ceramidase is upregulated in AML and represents a novel therapeutic target. Oncotarget. 2016 Dec 13;7:83208–83222.
  • Dick TE, Hengst JA, Fox TE, et al. The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines. J Pharmacol Exp Ther. 2015;352:494–508.
  • Chen L, Luo LF, Lu J, et al. FTY720 induces apoptosis of M2 subtype acute myeloid leukemia cells by targeting sphingolipid metabolism and increasing endogenous ceramide levels. Plos One. 2014;9:e103033.
  • Morad SA, Davis TS, Kester M, et al. Dynamics of ceramide generation and metabolism in response to fenretinide–diversity within and among leukemia. Leuk Res. 2015;39:1071–1078.
  • Dany M, Gencer S, Nganga R, et al. Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML. Blood. 2016 Oct 13;128:1944–1958.
  • Chapman JV, Gouaze-Andersson V, Messner MC, et al. Metabolism of short-chain ceramide by human cancer cells–implications for therapeutic approaches. Biochem Pharmacol. 2010 Aug 01;80:308–315.
  • Morad SA, Ryan TE, Neufer PD, et al. Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia. J Lipid Res. 2016 Jul;57:1231–1242.
  • Morad SA, Davis TS, MacDougall MR, et al. Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer. Biochem Pharmacol. 2017 Apr 15;130:21-33.
  • Morad SA, Cabot MC. Tamoxifen regulation of sphingolipid metabolism–therapeutic implications. Biochim Biophys Acta. 2015 Sep;1851:1134–1145.
  • Brown TJ, Garcia AM, Kissinger LN, et al. Therapeutic combination of nanoliposomal safingol and nanoliposomal ceramide for acute myeloid leukemia. J Leuk. 2013;1:110.
  • Paugh SW, Paugh BS, Rahmani M, et al. A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia. Blood. 2008 Aug 15;112:1382–1391.
  • Hengst JA, Wang X, Sk UH, et al. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg Med Chem Lett. 2010 Dec 15;20:7498–7502.
  • Shtraizent N, Eliyahu E, Park JH, et al. Autoproteolytic cleavage and activation of human acid ceramidase. J Biol Chem. 2008 Apr 25;283:11253–11259.
  • Frohbergh M, He X, Schuchman EH. The molecular medicine of acid ceramidase. Biol Chem. 2015 Jun;396:759–765.
  • Raisova M, Goltz G, Bektas M, et al. Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes. FEBS Lett. 2002 Apr 10;516:47–52.
  • Musumarra G, Barresi V, Condorelli DF, et al. A bioinformatic approach to the identification of candidate genes for the development of new cancer diagnostics. Biol Chem. 2003;384:321–327.
  • Zeidan YH, Jenkins RW, Korman JB, et al. Molecular targeting of acid ceramidase: implications to cancer therapy. Curr Drug Targets. 2008;9:653–661.
  • Liu X, Cheng JC, Turner LS, et al. Acid ceramidase upregulation in prostate cancer: role in tumor development and implications for therapy. Expert Opin Ther Targets. 2009;13:1449–1458.
  • Realini N, Palese F, Pizzirani D, et al. Acid ceramidase in melanoma: expression, localization, and effects of pharmacological inhibition. J Biol Chem. 2016 Jan 29;291:2422–2434.
  • Morad SA, Levin JC, Tan SF, et al. Novel off-target effect of tamoxifen–inhibition of acid ceramidase activity in cancer cells. Biochim Biophys Acta. 2013;1831:1657–1664.
  • Hu X, Yang D, Zimmerman M, et al. IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia. Cancer Res. 2011 Apr 15;71:2882–2891.
  • Evangelisti C, Evangelisti C, Buontempo F, et al. Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies. Leukemia. 2016;30:2142–2151.
  • Alvarez SE, Harikumar KB, Hait NC, et al. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature. 2010 Jun 24;465:1084–1088.
  • Newton J, Lima S, Maceyka M, et al. Revisiting the sphingolipid rheostat: evolving concepts in cancer therapy. Exp Cell Res. 2015 May 01;333:195–200.
  • Li QF, Wu CT, Guo Q, et al. Sphingosine 1-phosphate induces Mcl-1 upregulation and protects multiple myeloma cells against apoptosis. Biochem Biophys Res Commun. 2008 Jun 20;371:159–162.
  • Watters RJ, Fox TE, Tan SF, et al. Targeting glucosylceramide synthase synergizes with C6-ceramide nanoliposomes to induce apoptosis in natural killer cell leukemia. Leuk Lymphoma. 2013;54:1288–1296.
  • Nica AF, Tsao CC, Watt JC, et al. Ceramide promotes apoptosis in chronic myelogenous leukemia-derived K562 cells by a mechanism involving caspase-8 and JNK. Cell Cycle. 2008 Nov 01;7:3362–3370.
  • Coe GL, Redd PS, Paschall AV, et al. Ceramide mediates FasL-induced caspase 8 activation in colon carcinoma cells to enhance FasL-induced cytotoxicity by tumor-specific cytotoxic T lymphocytes. Sci Rep. 2016 Aug 04;6:30816.
  • Holman DH, Turner LS, El-Zawahry A, et al. Lysosomotropic acid ceramidase inhibitor induces apoptosis in prostate cancer cells. Cancer Chemother Pharmacol. 2008;61:231–242.
  • Elojeimy S, Liu X, McKillop JC, et al. Role of acid ceramidase in resistance to FasL: therapeutic approaches based on acid ceramidase inhibitors and FasL gene therapy. Mol Ther. 2007;15:1259–1263.
  • Chipuk JE, Bouchier-Hayes L, Green DR. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ. 2006 Aug;13:1396–1402.
  • Leverson JD, Zhang H, Chen J, et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis. 2015 Jan 15;6:e1590.
  • Gores GJ, Kaufmann SH. Selectively targeting Mcl-1 for the treatment of acute myelogenous leukemia and solid tumors. Genes Dev. 2012 Feb 15;26:305–311.
  • Doi K, Liu Q, Gowda K, et al. Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression. Cancer Biol Ther. 2014;15:1077–1086.
  • Casson L, Howell L, Mathews LA, et al. Inhibition of ceramide metabolism sensitizes human leukemia cells to inhibition of BCL2-like proteins. Plos One. 2013;8:e54525.
  • Bedia C, Casas J, Garcia V, et al. Synthesis of a novel ceramide analogue and its use in a high-throughput fluorogenic assay for ceramidases. Chembiochem. 2007 Apr 16;8:642–648.
  • Xia Z, Draper JM, Smith CD. Improved synthesis of a fluorogenic ceramidase substrate. Bioorg Med Chem. 2010 Feb;18:1003–1009.
  • Camacho L, Meca-Cortes O, Abad JL, et al. Acid ceramidase as a therapeutic target in metastatic prostate cancer. J Lipid Res. 2013 May;54:1207–1220.
  • Bedia C, Camacho L, Abad JL, et al. A simple fluorogenic method for determination of acid ceramidase activity and diagnosis of Farber disease. J Lipid Res. 2010 Dec;51:3542–3547.
  • Eliyahu E, Shtraizent N, Shalgi R, et al. Construction of conditional acid ceramidase knockout mice and in vivo effects on oocyte development and fertility. Cell Physiol Biochem. 2012;30:735–748.
  • Draper JM, Xia Z, Smith RA, et al. Discovery and evaluation of inhibitors of human ceramidase. Mol Cancer Ther. 2011;10:2052–2061.
  • Saied EM, Arenz C. Inhibitors of ceramidases. Chem Phys Lipids. 2016 May;197:60–68.
  • Bai A, Szulc ZM, Bielawski J, et al. Synthesis and bioevaluation of omega-N-amino analogs of B13. Bioorg Med Chem. 2009 Mar 01;17:1840–1848.
  • Bai A, Szulc ZM, Bielawski J, et al. Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs. Bioorg Med Chem. 2014 Dec 15;22:6933–6944.
  • Canals D, Perry DM, Jenkins RW, et al. Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases. Br J Pharmacol. 2011;163:694–712.
  • Cheng JC, Bai A, Beckham TH, et al. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse. J Clin Invest. 2013;123:4344–4358.
  • Korbelik M, Banath J, Zhang W, et al. Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy-generated vaccine. Int J Cancer. 2016 Sep 15;139:1372–1378.
  • Bach A, Pizzirani D, Realini N, et al. Benzoxazolone carboxamides as potent acid ceramidase inhibitors: synthesis and structure-activity relationship (SAR) studies. J Med Chem. 2015 Dec 10;58:9258–9272.
  • Pizzirani D, Bach A, Realini N, et al. Benzoxazolone carboxamides: potent and systemically active inhibitors of intracellular acid ceramidase. Angew Chem Int Ed Engl. 2015 Jan 07;54:485–489.
  • Eliyahu E, Shtraizent N, He X, et al. Identification of cystatin SA as a novel inhibitor of acid ceramidase. J Biol Chem. 2011 Oct 14;286:35624–35633.
  • Morad SA, Tan SF, Feith DJ, et al. Modification of sphingolipid metabolism by tamoxifen and N-desmethyltamoxifen in acute myelogenous leukemia–Impact on enzyme activity and response to cytotoxics. Biochim Biophys Acta. 2015;1851:919–928.
  • Bedia C, Casas J, Andrieu-Abadie N, et al. Acid ceramidase expression modulates the sensitivity of A375 melanoma cells to dacarbazine. J Biol Chem. 2011 Aug 12;286:28200–28209.
  • Pizzirani D, Pagliuca C, Realini N, et al. Discovery of a new class of highly potent inhibitors of acid ceramidase: synthesis and structure-activity relationship (SAR). J Med Chem. 2013 May 09;56:3518–3530.
  • Realini N, Solorzano C, Pagliuca C, et al. Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity. Sci Rep. 2013;3:1035.
  • Sakamoto J, Hamada C, Rahman M, et al. An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer. Jpn J Clin Oncol. 2005;35:536–544.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.