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• W2889968661 abstract "Precision medicine has recently emerged as a promising strategy for cancer therapy because it not only specifically targets cancer cells but it also does not have adverse effects on normal cells. Oligonucleotide aptamers are a class of small molecule ligands that can specifically bind to their targets on cell surfaces with high affinity. Aptamers have great potential in precision cancer therapy due to their unique physical, chemical, and biological properties. Therefore, aptamer technology has been widely investigated for biomedical and clinical applications. This review focuses on the potential applications of aptamer technology as a new tool for precision treatment of hematological malignancies, including leukemia, lymphoma, and multiple myeloma. Precision medicine has recently emerged as a promising strategy for cancer therapy because it not only specifically targets cancer cells but it also does not have adverse effects on normal cells. Oligonucleotide aptamers are a class of small molecule ligands that can specifically bind to their targets on cell surfaces with high affinity. Aptamers have great potential in precision cancer therapy due to their unique physical, chemical, and biological properties. Therefore, aptamer technology has been widely investigated for biomedical and clinical applications. This review focuses on the potential applications of aptamer technology as a new tool for precision treatment of hematological malignancies, including leukemia, lymphoma, and multiple myeloma. Currently, chemotherapy is the mainstay treatment for hematological malignancies.1Bose P. Grant S. Rational Combinations of Targeted Agents in AML.J. Clin. Med. 2015; 4: 634-664Crossref PubMed Google Scholar Although chemotherapy is effective in many cases, it can cause severe side effects in patients due to a lack of specificity. Therefore, cancer cell- or oncogene-selective therapeutic approaches have recently emerged, e.g., precision medicine, as a result of the advances in cancer genotyping and phenotyping studies. Precision medicine targets specific abnormalities within the cancer cell genome, proteome, and immunome and markers involved in cancer initiation, development, and growth.2Brábek J. Rosel D. Fernandes M. Pragmatic medicine in solid cancer: a translational alternative to precision medicine.OncoTargets Ther. 2016; 9: 1839-1855Crossref PubMed Scopus (2) Google Scholar, 3Workman P. de Bono J. Targeted Therapeutics for Cancer Treatment: Major Progress towards Personalised Molecular Medicine. Elsevier, 2008Google Scholar In contrast to conventional chemotherapy, precision medicine specifically targets the individual characteristics of each patient’s cancer phenotypic profile, resulting in significantly increased therapeutic efficacy and decreased non-specific toxicity. To date, precision medicine has been extensively applied in various cancers, especially hematological malignancies. The major approaches of precision medicine include the following: (1) cell-targeted chemotherapy to specifically deliver chemotherapeutic agents to the cells of interest without affecting normal tissues,4DiJoseph J.F. Armellino D.C. Boghaert E.R. Khandke K. Dougher M.M. Sridharan L. Kunz A. Hamann P.R. Gorovits B. Udata C. et al.Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies.Blood. 2004; 103: 1807-1814Crossref PubMed Scopus (213) Google Scholar, 5Dijoseph J.F. Dougher M.M. Armellino D.C. Evans D.Y. Damle N.K. Therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia.Leukemia. 2007; 21: 2240-2245Crossref PubMed Scopus (99) Google Scholar (2) gene therapy to specifically silence oncogenes,6Wilda M. Fuchs U. Wössmann W. Borkhardt A. Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference (RNAi).Oncogene. 2002; 21: 5716-5724Crossref PubMed Scopus (278) Google Scholar, 7Sampson V.B. Rong N.H. Han J. Yang Q. Aris V. Soteropoulos P. Petrelli N.J. Dunn S.P. Krueger L.J. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells.Cancer Res. 2007; 67: 9762-9770Crossref PubMed Scopus (600) Google Scholar (3) immunotherapy to harness the power of the immune system in eliminating cancers,8Porter D.L. Levine B.L. Kalos M. Bagg A. June C.H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.N. Engl. J. Med. 2011; 365: 725-733Crossref PubMed Scopus (1978) Google Scholar, 9McClanahan F. Hanna B. Miller S. Clear A.J. Lichter P. Gribben J.G. Seiffert M. PD-L1 checkpoint blockade prevents immune dysfunction and leukemia development in a mouse model of chronic lymphocytic leukemia.Blood. 2015; 126: 203-211Crossref PubMed Scopus (70) Google Scholar and (4) cell-specific biotherapies to inhibit cancer development by stimulating relevant cellular signaling pathways.10Uckun F.M. Evans W.E. Forsyth C.J. Waddick K.G. Ahlgren L.T. Chelstrom L.M. Burkhardt A. Bolen J. Myers D.E. Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases.Science. 1995; 267: 886-891Crossref PubMed Google Scholar Precision medicine has shown great potential and perspective in the clinical treatment of cancer as a result of the recent technological advances. Aptamers are short, single-stranded oligonucleotides (RNA or single-stranded DNA [ssDNA], respectively), usually 20–80 nt in length with a tridimensional folded structure. Aptamers are highly specific and bind tightly to their targets after structural recognition (Figure 1), in a manner similar to antibodies binding to their antigens.11Catuogno S. Esposito C.L. Condorelli G. de Franciscis V. Nucleic acids delivering nucleic acids.Adv. Drug Deliv. Rev. 2018; (Published online April 6, 2018)https://doi.org/10.1016/j.addr.2018.04.006Crossref PubMed Scopus (17) Google Scholar In 1990, Ellington and Szostak12Ellington A.D. Szostak J.W. In vitro selection of RNA molecules that bind specific ligands.Nature. 1990; 346: 818-822Crossref PubMed Scopus (6121) Google Scholar coined the term aptamer for this unique class of nucleic acids; the term derives from the Latin word aptus, which means fit, and the Greek word meros, which means part. To date, aptamers have been developed for a wide range of targets, including small metal ions or molecules, peptides, proteins, bacteria, viruses, whole cells, and targets within live animals.13Zhou G. Latchoumanin O. Hebbard L. Duan W. Liddle C. George J. Qiao L. Aptamers as targeting ligands and therapeutic molecules for overcoming drug resistance in cancers.Adv. Drug Deliv. Rev. 2018; (Published online April 6, 2018)https://doi.org/10.1016/j.addr.2018.04.005Crossref Scopus (17) Google Scholar Aptamers have been widely used in the diagnosis and treatment of various diseases.14Liu Z. Chen W. Han Y. Ouyang J. Chen M. Hu S. Deng L. Liu Y.N. A label-free sensitive method for membrane protein detection based on aptamer and AgNCs transfer.Talanta. 2017; 175: 470-476Crossref PubMed Scopus (4) Google Scholar, 15Wang Z. Ding J. Luo S. Wang P. Liang Q. [Development and evaluation of ultrasound contrast agents with AS1411-conjugated nanoparticles with liquid core].Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018; 43: 610-618PubMed Google Scholar, 16Luo S. Wang S. Luo N. Chen F. Hu C. Zhang K. The application of aptamer 5TR1 in triple negative breast cancer target therapy.J. Cell. Biochem. 2018; 119: 896-908Crossref PubMed Scopus (1) Google Scholar, 17Liu X. Qin Y. Deng C. Xiang J. Li Y. A simple and sensitive impedimetric aptasensor for the detection of tumor markers based on gold nanoparticles signal amplification.Talanta. 2015; 132: 150-154Crossref PubMed Scopus (30) Google Scholar Oligonucleotide aptamers present the following significant advantages compared to protein antibodies:(1)Higher tissue permeability. Aptamers have significantly smaller molecular weights (8–25 kDa) compared to antibodies (over 150 kDa);18Sun H. Zhu X. Lu P.Y. Rosato R.R. Tan W. Zu Y. Oligonucleotide aptamers: new tools for targeted cancer therapy.Mol. Ther. Nucleic Acids. 2014; 3: e182Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar thus, they can penetrate tissue membranes and reach their target sites more efficiently in vivo compared to antibodies, with dissociation constants (Kd) in the pico- to nanomolar range.19Nimjee S.M. Rusconi C.P. Sullenger B.A. Aptamers: an emerging class of therapeutics.Annu. Rev. Med. 2005; 56: 555-583Crossref PubMed Scopus (717) Google Scholar, 20Gupta S. Hirota M. Waugh S.M. Murakami I. Suzuki T. Muraguchi M. Shibamori M. Ishikawa Y. Jarvis T.C. Carter J.D. et al.Chemically modified DNA aptamers bind interleukin-6 with high affinity and inhibit signaling by blocking its interaction with interleukin-6 receptor.J. Biol. Chem. 2014; 289: 8706-8719Crossref PubMed Scopus (73) Google Scholar Nonetheless, the smaller molecular weights of aptamers render them susceptible to rapid excretion through renal filtration in vivo.21Dass C.R. Saravolac E.G. Li Y. Sun L.Q. Cellular uptake, distribution, and stability of 10-23 deoxyribozymes.Antisense Nucleic Acid Drug Dev. 2002; 12: 289-299Crossref PubMed Google Scholar During the last decade, chemical modification strategies to prevent renal clearance of aptamers have emerged, and they have significantly increased the half-life of aptamers in vivo.22Ni S. Yao H. Wang L. Lu J. Jiang F. Lu A. Zhang G. Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes.Int. J. Mol. Sci. 2017; 18: 1683Crossref PubMed Scopus (16) Google Scholar Da Pieve et al.23Da Pieve C. Blackshaw E. Missailidis S. Perkins A.C. PEGylation and biodistribution of an anti-MUC1 aptamer in MCF-7 tumor-bearing mice.Bioconjug. Chem. 2012; 23: 1377-1381Crossref PubMed Scopus (39) Google Scholar reported that conjugation of the murine PD-1 aptamer to a high-molecular-weight polyethylene glycol (PEG) significantly limited the rate of renal filtration, and it increased the half-life of the aptamer from 1 to 24–48 hr in vivo. Thus, modified aptamers can exhibit high bioavailability in clinical applications, given that they readily reach their targets, and they can remain in the bloodstream for extended time periods in vivo.(2)Easy to modify and low cost. Due to their simpler structures compared to antibodies, aptamers can be easily modified through chemical processes, enabling easier optimization of their clinical properties, such as resistance to nuclease degradation24Shaw J.P. Kent K. Bird J. Fishback J. Froehler B. Modified deoxyoligonucleotides stable to exonuclease degradation in serum.Nucleic Acids Res. 1991; 19: 747-750Crossref PubMed Google Scholar, 25de Smidt P.C. Le Doan T. de Falco S. van Berkel T.J. Association of antisense oligonucleotides with lipoproteins prolongs the plasma half-life and modifies the tissue distribution.Nucleic Acids Res. 1991; 19: 4695-4700Crossref PubMed Google Scholar, 26Peng C.G. Damha M.J. G-quadruplex induced stabilization by 2′-deoxy-2′-fluoro-D-arabinonucleic acids (2'F-ANA).Nucleic Acids Res. 2007; 35: 4977-4988Crossref PubMed Scopus (72) Google Scholar or increased half-life27Dougan H. Lyster D.M. Vo C.V. Stafford A. Weitz J.I. Hobbs J.B. Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood.Nucl. Med. Biol. 2000; 27: 289-297Crossref PubMed Scopus (0) Google Scholar, 28Van Eijk L. Swinkels D.W. John A. Schwoebel F. Fliegert F. Summo L. Vauleon S. Laarakkers J.M. Riecke K. Pickkers P. Randomized double-blind placebo-controlled PK/PD study on the effects of a single intravenous dose of the anti-hepcidin Spiegelmer NOX-H94 on serum iron during experimental human endotoxemia.Crit. Care. 2013; 17: P352Crossref Google Scholar in vivo. Aptamers can be linked with drugs, radioisotopes, RNA oligonucleotides, or even nanostructures to specifically deliver anticancer agents for targeted therapy.29McNamara 2nd, J.O. Andrechek E.R. Wang Y. Viles K.D. Rempel R.E. Gilboa E. Sullenger B.A. Giangrande P.H. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras.Nat. Biotechnol. 2006; 24: 1005-1015Crossref PubMed Scopus (752) Google Scholar, 30Orava E.W. Cicmil N. Gariépy J. Delivering cargoes into cancer cells using DNA aptamers targeting internalized surface portals.Biochim. Biophys. Acta. 2010; 1798: 2190-2200Crossref PubMed Google Scholar, 31Kanwar J.R. Roy K. Kanwar R.K. Chimeric aptamers in cancer cell-targeted drug delivery.Crit. Rev. Biochem. Mol. Biol. 2011; 46: 459-477Crossref PubMed Google Scholar Additionally, aptamers are rapidly produced on a large scale by methods adhering to good manufacturing practices (GMPs), and they have lower production costs compared to antibodies. In light of the aforementioned advantages, aptamers are very promising, and they have great potential in clinical applications, rendering them a powerful tool in precision therapy of hematological malignancies. Recent advances in aptamer-based precision medicine show its superior therapeutic effects in cancer treatment as compared to conventional strategies. Each year, the increasing number of reports underscores the major advances of aptamer-based precision medicine, including biotherapy,32Mahlknecht G. Maron R. Mancini M. Schechter B. Sela M. Yarden Y. Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth.Proc. Natl. Acad. Sci. USA. 2013; 110: 8170-8175Crossref PubMed Scopus (74) Google Scholar cell-selective chemotherapy,33Huang Y.F. Shangguan D. Liu H. Phillips J.A. Zhang X. Chen Y. Tan W. Molecular assembly of an aptamer-drug conjugate for targeted drug delivery to tumor cells.ChemBioChem. 2009; 10: 862-868Crossref PubMed Scopus (256) Google Scholar, 34Taghdisi S.M. Danesh N.M. Sarreshtehdar Emrani A. Tabrizian K. Zandkarimi M. Ramezani M. Abnous K. Targeted delivery of Epirubicin to cancer cells by PEGylated A10 aptamer.J. Drug Target. 2013; 21: 739-744Crossref PubMed Scopus (0) Google Scholar oncogene-specific gene therapy,29McNamara 2nd, J.O. Andrechek E.R. Wang Y. Viles K.D. Rempel R.E. Gilboa E. Sullenger B.A. Giangrande P.H. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras.Nat. Biotechnol. 2006; 24: 1005-1015Crossref PubMed Scopus (752) Google Scholar, 35Dai F. Zhang Y. Zhu X. Shan N. Chen Y. Anticancer role of MUC1 aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation.Target. Oncol. 2012; 7: 217-225Crossref PubMed Scopus (49) Google Scholar targeted nanomedicine,36Guo J. Gao X. Su L. Xia H. Gu G. Pang Z. Jiang X. Yao L. Chen J. Chen H. Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery.Biomaterials. 2011; 32: 8010-8020Crossref PubMed Scopus (373) Google Scholar, 37Liao J. Liu B. Liu J. Zhang J. Chen K. Liu H. Cell-specific aptamers and their conjugation with nanomaterials for targeted drug delivery.Expert Opin. Drug Deliv. 2015; 12: 493-506Crossref PubMed Scopus (16) Google Scholar, 38Zhou W. Zhou Y. Wu J. Liu Z. Zhao H. Liu J. Ding J. Aptamer-nanoparticle bioconjugates enhance intracellular delivery of vinorelbine to breast cancer cells.J. Drug Target. 2014; 22: 57-66Crossref PubMed Scopus (21) Google Scholar and immunotherapy (Table 1; Figure 2).39McNamara J.O. Kolonias D. Pastor F. Mittler R.S. Chen L. Giangrande P.H. Sullenger B. Gilboa E. Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice.J. Clin. Invest. 2008; 118: 376-386Crossref PubMed Scopus (194) Google Scholar, 40Lai W.-Y. Huang B.-T. Wang J.-W. Lin P.-Y. Yang P.-C. A Novel PD-L1-targeting Antagonistic DNA Aptamer With Antitumor Effects.Mol. Ther. Nucleic Acids. 2016; 5: e397Abstract Full Text Full Text PDF PubMed Google ScholarTable 1Aptamers Specifically Targeting Cell Surface Biomarkers Studied for Precision Cancer TherapyApproachMechanismEffectBiotherapyaptamer interacts with surface markers and triggers intracellular signaling of cancer cells32Mahlknecht G. Maron R. Mancini M. Schechter B. Sela M. Yarden Y. Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth.Proc. Natl. Acad. Sci. USA. 2013; 110: 8170-8175Crossref PubMed Scopus (74) Google Scholarinduces activation of signaling pathway to regulate apoptosis or death of targeted cellsCell-selective chemotherapyas a targeting ligand, the aptamer is linked with chemotherapeutic agents, such as Dox,33Huang Y.F. Shangguan D. Liu H. Phillips J.A. Zhang X. Chen Y. Tan W. Molecular assembly of an aptamer-drug conjugate for targeted drug delivery to tumor cells.ChemBioChem. 2009; 10: 862-868Crossref PubMed Scopus (256) Google Scholar or functional linkers, such as polyethylene glycol34Taghdisi S.M. Danesh N.M. Sarreshtehdar Emrani A. Tabrizian K. Zandkarimi M. Ramezani M. Abnous K. Targeted delivery of Epirubicin to cancer cells by PEGylated A10 aptamer.J. Drug Target. 2013; 21: 739-744Crossref PubMed Scopus (0) Google Scholarincreases half-life and payload capacity of chemotherapeutic agents, with enhanced anticancer effects and fewer toxic side effectsGene therapyas a targeting ligand, the aptamer is linked to siRNA29McNamara 2nd, J.O. Andrechek E.R. Wang Y. Viles K.D. Rempel R.E. Gilboa E. Sullenger B.A. Giangrande P.H. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras.Nat. Biotechnol. 2006; 24: 1005-1015Crossref PubMed Scopus (752) Google Scholar or miRNA,35Dai F. Zhang Y. Zhu X. Shan N. Chen Y. Anticancer role of MUC1 aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation.Target. Oncol. 2012; 7: 217-225Crossref PubMed Scopus (49) Google Scholar and it forms aptamer-RNA chimerasspecific delivery of siRNA or miRNA into target cells to silence pathogenic oncogenesTargeted nanomedicineas a targeting ligand, the aptamer is linked with nanoparticles36Guo J. Gao X. Su L. Xia H. Gu G. Pang Z. Jiang X. Yao L. Chen J. Chen H. Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery.Biomaterials. 2011; 32: 8010-8020Crossref PubMed Scopus (373) Google Scholar, 37Liao J. Liu B. Liu J. Zhang J. Chen K. Liu H. Cell-specific aptamers and their conjugation with nanomaterials for targeted drug delivery.Expert Opin. Drug Deliv. 2015; 12: 493-506Crossref PubMed Scopus (16) Google Scholar, 38Zhou W. Zhou Y. Wu J. Liu Z. Zhao H. Liu J. Ding J. Aptamer-nanoparticle bioconjugates enhance intracellular delivery of vinorelbine to breast cancer cells.J. Drug Target. 2014; 22: 57-66Crossref PubMed Scopus (21) Google Scholarincreases circulation half-life, payload capacity, and target drug deliveryImmunotherapyas a targeting ligand, aptamer directly activates immune costimulatory molecules,39McNamara J.O. Kolonias D. Pastor F. Mittler R.S. Chen L. Giangrande P.H. Sullenger B. Gilboa E. Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice.J. Clin. Invest. 2008; 118: 376-386Crossref PubMed Scopus (194) Google Scholar suppresses immune checkpoint signaling,40Lai W.-Y. Huang B.-T. Wang J.-W. Lin P.-Y. Yang P.-C. A Novel PD-L1-targeting Antagonistic DNA Aptamer With Antitumor Effects.Mol. Ther. Nucleic Acids. 2016; 5: e397Abstract Full Text Full Text PDF PubMed Google Scholar or recruits immune cells to target cellsprecisely amplifies our immune system to fight malignancies Open table in a new tab Hematologic malignancies are types of cancer that begin in the blood-forming tissue, such as the bone marrow or the cells of the immune system. Historically, hematological malignancies comprise leukemia, lymphoma, and multiple myeloma (MM), a classification that is in accord with the WHO.41Swerdlow S.H. Campo E. Harris N.L. Jaffe E.S. Pileri S.A. Stein H. Thiele J. Vardiman J.W. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, 2008Google Scholar Herein we focus on recent advances in the applications of aptamers as therapeutic agents of hematological malignancies. Leukemia is a broad term for a group of cancers originating from hematopoietic stem cells; it is characterized by uncontrolled proliferation of undifferentiated white blood cells in peripheral blood and bone marrow.42Fröhling S. Scholl C. Gilliland D.G. Levine R.L. Genetics of myeloid malignancies: pathogenetic and clinical implications.J. Clin. Oncol. 2005; 23: 6285-6295Crossref PubMed Scopus (0) Google Scholar As the abnormal cells cannot develop further, they accumulate over time to substitute normal blood cells; this causes various symptoms correlated with dysfunction of blood cells, including anemia, bleeding, bruising, fatigue, fever, and enhanced risk of infections.43Jaffe E.S. Harris N.L. Stein H. Vardiman J.W. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, 2001Google Scholar Leukemias are generally classified into four main categories, depending on the disease progression and type of blood cells that are affected: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Currently, chemotherapy is the mainstream treatment for leukemia.1Bose P. Grant S. Rational Combinations of Targeted Agents in AML.J. Clin. Med. 2015; 4: 634-664Crossref PubMed Google Scholar However, chemotherapeutic agents lack selectivity between tumors and normal tissues, which results in serious side effects such as toxicity, limited drug concentration in cancer cells, and reduced therapeutic efficacy.44Yeung C.C.S. Radich J. Predicting Chemotherapy Resistance in AML.Curr. Hematol. Malig. Rep. 2017; 12: 530-536Crossref PubMed Scopus (1) Google Scholar AML is a type of malignant disorder originating from rapid clonal expansion of undifferentiated myeloid precursors,45Papaemmanuil E. Gerstung M. Bullinger L. Gaidzik V.I. Paschka P. Roberts N.D. Potter N.E. Heuser M. Thol F. Bolli N. et al.Genomic classification and prognosis in acute myeloid leukemia.N. Engl. J. Med. 2016; 374: 2209-2221Crossref PubMed Scopus (983) Google Scholar and it is currently treated with chemotherapy, despite the possibility of causing severe non-specific toxicity to normal tissues.46Döhner H. Weisdorf D.J. Bloomfield C.D. Acute Myeloid Leukemia.N. Engl. J. Med. 2015; 373: 1136-1152Crossref PubMed Scopus (898) Google Scholar Recent studies demonstrated that aptamer-mediated precision therapy has considerable efficacy in the treatment of AML. AS1411, the first ssDNA aptamer to undergo clinical trials, proved to be safe and well tolerated in patients;47Mongelard F. Bouvet P. AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia.Curr. Opin. Mol. Ther. 2010; 12: 107-114PubMed Google Scholar, 48Bates P.J. Laber D.A. Miller D.M. Thomas S.D. Trent J.O. Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer.Exp. Mol. Pathol. 2009; 86: 151-164Crossref PubMed Scopus (459) Google Scholar it can specifically target nucleolin, which is overexpressed in the cytoplasm and on membranes of various cancer cells, including AML.49Soundararajan S. Wang L. Sridharan V. Chen W. Courtenay-Luck N. Jones D. Spicer E.K. Fernandes D.J. Plasma membrane nucleolin is a receptor for the anticancer aptamer AS1411 in MV4-11 leukemia cells.Mol. Pharmacol. 2009; 76: 984-991Crossref PubMed Scopus (0) Google Scholar Chen et al.50Chen W. Sridharan V. Soundararajan S. Otake Y. Stuart R. Jones D. Fernandes D. Activity and Mechanism of Action of AS1411 in Acute Myeloid Leukemia Cells.Blood. 2007; 110: 1604Google Scholar reported that AS1411 significantly inhibited cell growth and reduced viability of the AML cell line MV4-11 and AML patient cells. Additional experiments revealed the mechanism by which AS1411 interfered with bcl-2 mRNA, an important anti-apoptotic factor, playing a crucial role in the stabilization of nucleolin.50Chen W. Sridharan V. Soundararajan S. Otake Y. Stuart R. Jones D. Fernandes D. Activity and Mechanism of Action of AS1411 in Acute Myeloid Leukemia Cells.Blood. 2007; 110: 1604Google Scholar The phase I clinical trial, completed in 2006, confirmed the safety and good tolerance of AS1411.51Storck S. Shukla M. Dimitrov S. Bouvet P. Functions of the histone chaperone nucleolin in diseases.Subcell. Biochem. 2007; 41: 125-144Crossref PubMed Google Scholar Furthermore, the phase II study (ClinicalTrials.gov: NCT00512083) demonstrated the synergistic anticancer effects of AS1411 with cytarabine in the treatment of AML, thus rendering it a promising candidate for AML therapy.47Mongelard F. Bouvet P. AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia.Curr. Opin. Mol. Ther. 2010; 12: 107-114PubMed Google Scholar In addition to their role as direct, targeted biotherapeutics, aptamers can function as effective vehicles carrying drugs and target biomarkers on hematopoietic cells.52Woźniak J. Kopeć-Szlezak J. c-Kit receptor (CD117) expression on myeloblasts and white blood cell counts in acute myeloid leukemia.Cytometry B Clin. Cytom. 2004; 58: 9-16Crossref PubMed Google Scholar Recently, Zhao et al.53Wells S.J. Bray R.A. Stempora L.L. Farhi D.C. CD117/CD34 expression in leukemic blasts.Am. J. Clin. Pathol. 1996; 106: 192-195Crossref PubMed Google Scholar developed a DNA aptamer specifically targeting CD117, a biomarker highly expressed by certain AML cells.54Ahmadi A. Poorfathollah A.-A. Aghaiipour M. Rezaei M. Nikoo-ghoftar M. Abdi M. Gharib A. Amini A. Diagnostic value of CD117 in differential diagnosis of acute leukemias.Tumour Biol. 2014; 35: 6763-6768Crossref PubMed Scopus (0) Google Scholar, 55Zhao N. Pei S.-N. Qi J. Zeng Z. Iyer S.P. Lin P. Tung C.H. Zu Y. Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid leukemia.Biomaterials. 2015; 67: 42-51Crossref PubMed Scopus (38) Google Scholar For the therapeutic study, the aptamer was conjugated with methotrexate (MTX) to generate Apt-MTX conjugates. This Apt-MTX conjugate showed significantly enhanced inhibition of cellular growth, triggered cell apoptosis, and induced G1 phase cell-cycle arrest of the AML cell line HEL and primary AML cells from patients, compared to MTX treatment alone, with negligible toxicity on off-target cells.53Wells S.J. Bray R.A. Stempora L.L. Farhi D.C. CD117/CD34 expression in leukemic blasts.Am. J. Clin. Pathol. 1996; 106: 192-195Crossref PubMed Google Scholar Another well-characterized plasma membrane biomarker, CD123, which is highly expressed on 45%–95% of AML cells,56Du X. Ho M. Pastan I. New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cells.J. Immunother. 2007; 30: 607-613Crossref PubMed Scopus (84) Google Scholar has been associated with increased resistance to chemotherapeutic drugs,57Ehninger A. Kramer M. Röllig C. Thiede C. Bornhäuser M. von Bonin M. Wermke M. Feldmann A. Bachmann M. Ehninger G. Oelschlägel U. Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia.Blood Cancer J. 2014; 4: e218Crossref PubMed Scopus (89) Google Scholar higher relapse rates, or poor prognosis58Thokala R. Olivares S. Mi T. Maiti S. Deniger D. Huls H. Torikai H. Singh H. Champlin R.E. Laskowski T. et al.Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.PLoS ONE. 2016; 11: e0159477Crossref PubMed Scopus (26) Google Scholar of AML, thus rendering it an ideal target for AML treatment. Wu et al.59Wu H. Wang M. Dai B. Zhang Y. Yang Y. Li Q. Duan M. Zhang X. Wang X. Li A. Zhang L. Novel CD123-aptamer-originated targeted drug trains for selectively delivering cytotoxic agent to tumor cells in acute myeloid leukemia theranostics.Drug Deliv. 2017; 24: 1216-1229Crossref PubMed Scopus (1) Google Scholar developed the first CD123 aptamers (dubbed ZW25 and CY30), and they designed a novel CD123-aptamer-mediated targeted drug train (TDT) with effective, biocompatible, and high drug-loading capacity. These two CD123 aptamers bind to an epitope of CD123 peptide and CD123(+) AML cells with high specificity and minimal cross-reactivity to other proteins, such as albumin, IgG, or trypsin.59Wu H. Wang M. Dai B. Zhang Y. Yang Y. Li Q. Duan M. Zhang X. Wang X. Li A. Zhang L. Novel CD123-aptamer-originated targeted drug trains for selectively delivering cytotoxic agent to tumor cells in acute myeloid leukemia theranostics.Drug Deliv. 2017; 24: 1216-1229Crossref PubMed Scopus (1) Google Scholar The TDT transported a high load of Doxorubicin (Dox) to CD123+ cells with substantial efficacy, while significantly reducing drug toxicity to CD123− cells in vitro.58Thokala R. Olivares S. Mi T. Maiti S. Deniger D. Huls H. Torikai H. Singh H. Champlin R.E. Laskowski T. et al.Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.PLoS ONE. 2016; 11: e0159477Crossref PubMed Scopus (26) Google Scholar In addition, the TDT inhibited tumor growth of a mouse xenograft tumor model in vivo and prolonged their survival.59Wu H. Wang M. Dai B. Zhang Y. Yang Y. Li Q. Duan M. Zhang X. Wang X. Li A. Zhang L. Novel CD123-aptamer-originated targeted drug trains for selectively delivering cytotoxic agent to tumor cells in acute myeloid leukemia theranostics.Drug Deliv. 2017; 24: 1216-1229Crossref PubMed Scopus (1) Google Scholar In summary, these results suggest that aptamer and aptamer-mediated chemotherapies have high potential to selectively deliver cytotoxic agents to tar" @default.
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• W2889968661 date "2018-12-01" @default.
• W2889968661 modified "2023-10-15" @default.
• W2889968661 title "Oligonucleotide Aptamer-Mediated Precision Therapy of Hematological Malignancies" @default.
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