Targeting the mitochondria in acute myeloid leukemia
Tóm tắt
Acute myeloid leukemia (AML) is a clonal hematologic neoplasm characterized by heterogeneity of genetic abnormalities found at diagnosis. These abnormalities serve to classify patients by risk group into low, intermediate, and high risk. It also provides specific targets for the development of new combinational therapies. However, because of the heterogeneity of genetic abnormalities, targeted therapy is not always possible. Altered mitochondrial metabolism is a common feature in cancer cells, a phenomenon first described by Otto Warburg. In AML patients, the discovery of mutations in the isocitrate dehydrogenase gene provided for the first time a link between altered mitochondrial metabolism and AML. This raised the possibility of testing drugs known as mitocans for new combinational therapeutic approaches. Mitocans are a diverse group of anti-cancer compounds that target mitochondria. They disrupt energy production leading to enhanced generation of reactive oxygen species along with the activation of the intrinsic pathway of apoptosis. The present review discusses the different types of mitocans and their mechanism of action along with preclinical and clinical studies in AML.
Tài liệu tham khảo
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008.
Basak NP, Banerjee S. Mitochondrial dependency in progression of acute myeloid leukemia. Mitochondrion. 2015;21:41–8.
Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2009;115:453–74.
Röllig C, Bornhäuser M, Thiede C, Taube F, Kramer M, Mohr B, et al. Long-Term Prognosis of Acute Myeloid Leukemia According to the New Genetic Risk Classification of the European LeukemiaNet Recommendations: Evaluation of the Proposed Reporting System. J Clin Oncol. 2011;29:2758–65.
Jácomo RH, De Figueiredo-Pontes LL, Rego EM. Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda. Rev Assoc Med Bras. 2008;54:82–9.
Tomita A, Kiyoi H, Naoe T. Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) in acute promyelocytic leukemia. Int J Hematol. 2013;97:717–25.
Stone RM, Mandrekar S, Sanford BL, Geyer S, Bloomfield CD, Dohner K, et al. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]). Blood. 2015;126:6.
Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11:325–37.
Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 2011;144:646–74.
Kroemer G, Pouyssegur J. Tumor Cell Metabolism: Cancer’s Achilles’ Heel. Cancer Cell. 2008;13:472–82.
Leni Z, Parakkal G, Arcaro A. Emerging Metabolic Targets in the Therapy of Hematological Malignancies. BioMed Res Int. 2013;2013:1–12.
Marcucci G, Haferlach T, Döhner H. Molecular Genetics of Adult Acute Myeloid Leukemia: Prognostic and Therapeutic Implications. J Clin Oncol. 2011;29:475–86.
Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012;483:474–8.
Chen WL, Wang JH, Zhao AH, Xu X, Wang YH, Chen TL, et al. A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value. Blood. 2014;124:1645–54.
Neuzil J, Dong LF, Rohlena J, Truksa J, Ralph SJ. Classification of mitocans, anti-cancer drugs acting on mitochondria. Mitochondrion. 2013;13:199–208.
Rohlena J, Dong LF, Ralph SJ, Neuzil J. Anticancer Drugs Targeting the Mitochondrial Electron Transport Chain. Antioxid Redox Signal. 2011;15:2951–74.
Pelicano H, Martin DS, Xu RH, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene. 2006;25:4633–46.
Mathupala SP, Ko YH, Pedersen PL. Hexokinase II: Cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene. 2006;25:4777–86.
Soares Junior J, Porto Fonseca R, Cerci JJ, Buchpiguel CA, Livorsi da Cunha M, Mamed M, et al. Lista de recomendações do Exame PET/CT com 18F-FDG em Oncologia. Consenso entre a Sociedade Brasileira de Cancerologia e a Sociedade Brasileira de Biologia, Medicina Nuclear e Imagem Molecular. Radiol Bras. 2010;43:255–9.
Patra KC, Wang Q, Bhaskar PT, Miller L, Wang Z, Wheaton W, et al. Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer. Cancer Cell. 2013;24:213–28.
Kim W, Yoon JH, Jeong JM, Cheon GJ, Lee TS, Yang JI, et al. Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma. Mol Cancer Ther. 2007;6:2554–62.
Mathupala SP, Rempel A, Pedersen PL. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem. 2001;276:43407–12.
Liu LL, Long ZJ, Wang LX, Zheng FM, Fang ZG, Yan M, et al. Inhibition of mTOR Pathway Sensitizes Acute Myeloid Leukemia Cells to Aurora Inhibitors by Suppression of Glycolytic Metabolism. Mol Cancer Res. 2013;11:1326–36.
Fernandes MS, Reddy MM, Croteau NJ, Walz C, Weisbach H, Podar K, et al. Novel Oncogenic Mutations of CBL in Human Acute Myeloid Leukemia That Activate Growth and Survival Pathways Depend on Increased Metabolism. J Biol Chem. 2010;285:32596–605.
Tait SWG, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 2010;11:621–32.
Vo TT, Ryan J, Carrasco R, Neuberg D, Rossi DJ, Stone RM, et al. Relative Mitochondrial Priming of Myeloblasts and Normal HSCs Determines Chemotherapeutic Success in AML. Cell. 2012;151:344–55.
Rahmani M, Aust MM, Attkisson E, Williams DC, Ferreira-Gonzalez A, Grant S. Inhibition of Bcl-2 antiapoptotic members by obatoclax potently enhances sorafenib-induced apoptosis in human myeloid leukemia cells through a Bim-dependent process. Blood. 2012;119:6089–98.
Rahmani M, Aust MM, Hawkins E, Parker RE, Reshko L, Ross M, et al. Co-Administration of the mTORC1/TORC2 Inhibitor INK128 and the Bcl-2/Bcl-Xl Antagonist ABT-737 Kills Human Myeloid Leukemia Cells through Mcl-1 Down-Regulation and AKT Inactivation. Blood. 2015;126:3676.
Yeung M, Hurren R, Nemr C, Wang X, Hershenfeld S, Gronda M, et al. Mitochondrial DNA damage by bleomycin induces AML cell death. Apoptosis. 2015;20:811–20.
Škrtić M, Sriskanthadevan S, Jhas B, Gebbia M, Wang X, Wang Z, et al. Inhibition of Mitochondrial Translation as a Therapeutic Strategy for Human Acute Myeloid Leukemia. Cancer Cell. 2011;20:674–88.
Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia. N Engl J Med. 2013;369:111–21.
Chen G, Zhu J, Shi X, Ni J, Zhong H, Si G, et al. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood. 1996;88:1052–61.
Lu J, Chew E-H, Holmgren A. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc Natl Acad Sci U S A. 2007;104:12288–93.
de Thé H, Chen Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer. 2010;10:775–83.
Zhang Y, Sun M, Shi W, Yang Q, Chen C, Wang Z, et al. Arsenic trioxide suppresses transcription of hTERT through down-regulation of multiple transcription factors in HL-60 leukemia cells. Toxicol Lett. 2015;232:481–9.
Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, et al. Biología Celular y Molecular. 5°. Buenos Aires: Médica Panamericana; 2005.
dos Santos GAS, Lima RS A e, Pestana CR, Lima ASG, Scheucher PS, Thome CH, et al. (+)[alpha]-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo. Leukemia. 2012;26:451–60.
He L-Z, Tribioli C, Rivi R, Peruzzi D, Pelicci PG, Soares V, et al. Acute leukemia with promyelocytic features in PML/RARα transgenic mice. Proc Natl Acad Sci U S A. 1997;94:5302–7.