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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Review

Cancer stem cells in basic science and in translational oncology: can we translate into clinical application?

Published in: Journal of Hematology & Oncology | Issue 1/2015

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Abstract

Since their description and identification in leukemias and solid tumors, cancer stem cells (CSC) have been the subject of intensive research in translational oncology. Indeed, recent advances have led to the identification of CSC markers, CSC targets, and the preclinical and clinical evaluation of the CSC-eradicating (curative) potential of various drugs. However, although diverse CSC markers and targets have been identified, several questions remain, such as the origin and evolution of CSC, mechanisms underlying resistance of CSC against various targeted drugs, and the biochemical basis and function of stroma cell-CSC interactions in the so-called ‘stem cell niche.’ Additional aspects that have to be taken into account when considering CSC elimination as primary treatment-goal are the genomic plasticity and extensive subclone formation of CSC. Notably, various cell fractions with different combinations of molecular aberrations and varying proliferative potential may display CSC function in a given neoplasm, and the related molecular complexity of the genome in CSC subsets is considered to contribute essentially to disease evolution and acquired drug resistance. In the current article, we discuss new developments in the field of CSC research and whether these new concepts can be exploited in clinical practice in the future.
Literature
1.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.PubMed
2.
Ailles LE, Weissman IL. Cancer stem cells in solid tumors. Curr Opin Biotechnol. 2007;18:460–6.PubMed
3.
Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med. 2007;58:267–84.PubMed
4.
Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11:69–82.PubMed
5.
Dick JE. Stem cell concepts renew cancer research. Blood. 2008;112:4793–807.PubMed
6.
Cho RW, Clarke MF. Recent advances in cancer stem cells. Curr Opin Genet Dev. 2008;18:48–53.PubMed
7.
8.
Schulenburg A, Bramswig K, Herrmann H, Karlic H, Mirkina I, Hubmann R, et al. Neoplastic stem cells: current concepts and clinical perspectives. Crit Rev Oncol Hematol. 2010;76:79–98.PubMed
9.
Greaves M. Cancer stem cells: back to Darwin? Semin Cancer Biol. 2010;20(2):65–70.PubMed
10.
Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells - perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006;66:9339–44.PubMed
11.
Valent P. Emerging stem cell concepts for imatinib-resistant chronic myeloid leukaemia: implications for the biology, management, and therapy of the disease. Br J Haematol. 2008;142(3):361–78.PubMed
12.
Dick JE, Lapidot T. Biology of normal and acute myeloid leukemia stem cells. Int J Hematol. 2005;82:389–96.PubMed
13.
Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol. 2004;5:738–43.PubMed
14.
Konopleva MY, Jordan CT. Leukemia stem cells and microenvironment: biology and therapeutic targeting. J Clin Oncol. 2011;29:591–9.PubMed
15.
Sloma I, Jiang X, Eaves AC, Eaves CJ. Insights into the stem cells of chronic myeloid leukemia. Leukemia. 2010;24:1823–33.PubMed
16.
Roboz GJ, Guzman M. Acute myeloid leukemia stem cells: seek and destroy. Expert Rev Hematol. 2009;2:663–72.PubMed
17.
Holyoake TL, Jiang X, Jorgensen HG, Graham S, Alcorn MJ, Laird C, et al. Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with up-regulation of expression of interleukin-3. Blood. 2001;97:720–8.PubMed
18.
Copland M. Chronic myelogenous leukemia stem cells: what’s new? Curr Hematol Malig Rep. 2009;4:66–73.PubMed
19.
Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29:4741–51.PubMedCentralPubMed
20.
Donnenberg VS, Donnenberg AD. Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol. 2005;45:872–7.PubMed
21.
Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–84.PubMed
22.
Jiang X, Zhao Y, Smith C, Gasparetto M, Turhan A, Eaves A, et al. Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies. Leukemia. 2007;21:926–35.PubMed
23.
Barnes DJ, Melo JV. Primitive, quiescent and difficult to kill: the role of non-proliferating stem cells in chronic myeloid leukemia. Cell Cycle. 2006;5:2862–6.PubMed
24.
Welch JS. Mutation position within evolutionary subclonal architecture in AML. Semin Hematol. 2014;51:273–83.PubMed
25.
Wang M, Wang Y, Zhong J. Side population cells and drug resistance in breast cancer. Mol Med Rep. 2015;doi:10.3892/mmr.2015.3291.
26.
Preuner S, Mitterbauer G, Mannhalter C, Herndlhofer S, Sperr WR, Valent P, et al. Quantitative monitoring of BCR/ABL1 mutants for surveillance of subclone-evolution, -expansion, and -depletion in chronic myeloid leukaemia. Eur J Cancer. 2012;48:233–6.PubMed
27.
Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, et al. Identification of cells initiating human melanomas. Nature. 2008;451:345–9.PubMedCentralPubMed
28.
Valent P. Targeting of leukemia-initiating cells to develop curative drug therapies: straightforward but nontrivial concept. Curr Cancer Drug Targets. 2011;11(1):56–71.PubMed
29.
Frank NY, Schatton T, Frank MH. The therapeutic promise of the cancer stem cell concept. J Clin Invest. 2010;120:41–50.PubMedCentralPubMed
30.
Besancon R, Valsesia-Wittmann S, Puisieux A, de Fromentel CC, Maguer-Satta V. Cancer stem cells: the emerging challenge of drug targeting. Curr Med Chem. 2009;16:394–416.PubMed
31.
Korkaya H, Wicha MS. Selective targeting of cancer stem cells: a new concept in cancer therapeutics. BioDrugs. 2007;21:299–310.PubMed
32.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.PubMed
33.
Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.PubMed
34.
Civenni G, Walter A, Kobert N, Mihic-Probst D, Zipser M, Belloni B, et al. Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth. Cancer Res. 2011;71:3098–109.PubMed
35.
Pearson T, Greiner DL, Shultz LD. Creation of “humanized” mice to study human immunity. Curr Protoc Immunol. 2008;15(15):21.PubMed
36.
Ishikawa F, Saito Y, Yoshida S, Harada M, Shultz LD. The differentiative and regenerative properties of human hematopoietic stem/progenitor cells in NOD-SCID/IL2rgamma(null) mice. Curr Top Microbiol Immunol. 2008;324:87–94.PubMed
37.
Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008;456:593–8.PubMedCentralPubMed
38.
Taussig DC, Miraki-Moud F, Anjos-Afonso F, Pearce DJ, Allen K, Ridler C, et al. Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells. Blood. 2008;112:568–75.PubMed
39.
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313–23.PubMed
40.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–8.PubMedCentralPubMed
41.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.PubMed
42.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.PubMed
43.
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.PubMed
44.
Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008;13:153–66.PubMed
45.
Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol. 2007;25:1315–21.PubMed
46.
O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–10.PubMed
47.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.PubMed
48.
Bohm A, Herrmann H, Mitterbauer-Hohendanner G, Hauswirth AW, Rabitsch W, Mitterbauer M, et al. Stable non-transforming minimal residual disease in Philadelphia chromosome positive acute lymphoblastic leukemia after autologous transplantation: origin from neoplastic yet ‘pre-leukemic’ stem cells? Leuk Lymphoma. 2011;52:842–8.PubMed
49.
Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 2003;17:1253–70.PubMedCentralPubMed
50.
Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 2005;65:9328–37.PubMed
51.
Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977;91:335–44.PubMed
52.
Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A. 2003;100:15178–83.PubMedCentralPubMed
53.
Vermeulen L, Todaro M, de Sousa MF, Sprick MR, Kemper K, Perez Alea M, et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci U S A. 2008;105:13427–32.PubMedCentralPubMed
54.
Gerashchenko BI, Huna A, Erenpreisa J. Characterization of breast cancer DNA content profiles as a prognostic tool. Exp Oncol. 2014;36:219–25.PubMed
55.
Moserle L, Ghisi M, Amadori A, Indraccolo S. Side population and cancer stem cells: therapeutic implications. Cancer Lett. 2010;288:1–9.PubMed
56.
Fukaya R, Ohta S, Yamaguchi M, Fujii H, Kawakami Y, Kawase T, et al. Isolation of cancer stem-like cells from a side population of a human glioblastoma cell line, SK-MG-1. Cancer Lett. 2010;291:150–7.PubMed
57.
Murase M, Kano M, Tsukahara T, Takahashi A, Torigoe T, Kawaguchi S, et al. Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas. Br J Cancer. 2009;101:1425–32.PubMedCentralPubMed
58.
Li T, Su Y, Mei Y, Leng Q, Leng B, Liu Z, et al. ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients’ outcome. Lab Invest. 2010;90:234–44.PubMedCentralPubMed
59.
Ran D, Schubert M, Pietsch L, Taubert I, Wuchter P, Eckstein V, et al. Aldehyde dehydrogenase activity among primary leukemia cells is associated with stem cell features and correlates with adverse clinical outcomes. Exp Hematol. 2009;37:1423–34.PubMed
60.
Chen YC, Chen YW, Hsu HS, Tseng LM, Huang PI, Lu KH, et al. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun. 2009;385:307–13.PubMed
61.
Moreb JS. Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther. 2008;3:237–46.PubMed
62.
Polyak K, Hahn WC. Roots and stems: stem cells in cancer. Nat Med. 2006;12:296–300.PubMed
63.
Weissman IL, Shizuru JA. The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood. 2008;112:3543–53.PubMedCentralPubMed
64.
Florian S, Sonneck K, Hauswirth AW, Krauth MT, Schernthaner GH, Sperr WR, et al. Detection of molecular targets on the surface of CD34+/CD38– stem cells in various myeloid malignancies. Leuk Lymphoma. 2006;47:207–22.PubMed
65.
Moshaver B, van Rhenen A, Kelder A, van der Pol M, Terwijn M, Bachas C, et al. Identification of a small subpopulation of candidate leukemia initiating cells in the side population (SP) of patients with acute myeloid leukemia. Stem Cells. 2008;26(12):3059–67.PubMed
66.
Blair A, Hogge DE, Ailles LE, Lansdorp PM, Sutherland HJ. Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood. 1997;89:3104–12.PubMed
67.
van Rhenen A, van Dongen GA, Kelder A, Rombouts EJ, Feller N, Moshaver B, et al. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood. 2007;110:2659–66.PubMed
68.
Hosen N, Park CY, Tatsumi N, Oji Y, Sugiyama H, Gramatzki M, et al. CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci U S A. 2007;104:11008–13.PubMedCentralPubMed
69.
Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, et al. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia. 2000;14:1777–84.PubMed
70.
Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75:2417–26.PubMed
71.
Kitamura Y, Hirotab S. Kit as a human oncogenic tyrosine kinase. Cell Mol Life Sci. 2004;61:2924–31.PubMed
72.
Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12:1167–74.PubMed
73.
Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs Jr KD, et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138:286–99.PubMedCentralPubMed
74.
Kim JB, Ko E, Han W, Lee JE, Lee KM, Shin I, et al. CD24 cross-linking induces apoptosis in, and inhibits migration of, MCF-7 breast cancer cells. BMC Cancer. 2008;8:118.PubMedCentralPubMed
75.
Saito Y, Kitamura H, Hijikata A, Tomizawa-Murasawa M, Tanaka S, Takagi S, et al. Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Sci Transl Med. 2010;2:17ra19.
76.
Taussig DC, Pearce DJ, Simpson C, Rohatiner AZ, Lister TA, Kelly G, et al. Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood. 2005;106:4086–92.PubMedCentralPubMed
77.
Blatt K, Herrmann H, Hoermann G, Willmann M, Cerny-Reiterer S, Sadovnik I, et al. Identification of campath-1 (CD52) as novel drug target in neoplastic stem cells in 5q-patients with MDS and AML. Clin Cancer Res. 2014;20(13):3589–602.PubMed
78.
Taussig DC, Vargaftig J, Miraki-Moud F, Griessinger E, Sharrock K, Luke T, et al. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(−) fraction. Blood. 2010;115:1976–84.PubMedCentralPubMed
79.
Nilsson L, Astrand-Grundstrom I, Anderson K, Arvidsson I, Hokland P, Bryder D, et al. Involvement and functional impairment of the CD34(+)CD38(−)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood. 2002;100:259–67.PubMed
80.
De Smet D, Trullemans F, Jochmans K, Renmans W, Smet L, Heylen O, et al. Diagnostic potential of CD34+ cell antigen expression in myelodysplastic syndromes. Am J Clin Pathol. 2012;138:732–43.PubMed
81.
Nilsson L, Astrand-Grundstrom I, Arvidsson I, Jacobsson B, Hellstrom-Lindberg E, Hast R, et al. Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level. Blood. 2000;96:2012–21.PubMed
82.
Jamieson CH, Gotlib J, Durocher JA, Chao MP, Mariappan MR, Lay M, et al. The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci U S A. 2006;103:6224–9.PubMedCentralPubMed
83.
Kobayashi CI, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K, et al. The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. Blood. 2014;123:2540–9.PubMed
84.
Herrmann H, Sadovnik I, Cerny-Reiterer S, Rulicke T, Stefanzl G, Willmann M, et al. Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia. Blood. 2014;123(25):3951–62.PubMed
85.
Herrmann H, Cerny-Reiterer S, Gleixner KV, Blatt K, Herndlhofer S, Rabitsch W, et al. CD34(+)/CD38(−) stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin. Haematologica. 2012;97:219–26.PubMedCentralPubMed
86.
Nievergall E, Ramshaw HS, Yong AS, Biondo M, Busfield SJ, Vairo G, et al. Monoclonal antibody targeting of IL-3 receptor alpha with CSL362 effectively depletes CML progenitor and stem cells. Blood. 2014;123:1218–28.PubMed
87.
Jaras M, Johnels P, Hansen N, Agerstam H, Tsapogas P, Rissler M, et al. Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. Proc Natl Acad Sci U S A. 2010;107:16280–5.PubMedCentralPubMed
88.
Cobaleda C, Gutierrez-Cianca N, Perez-Losada J, Flores T, Garcia-Sanz R, Gonzalez M, et al. A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia. Blood. 2000;95:1007–13.PubMed
89.
Kong Y, Yoshida S, Saito Y, Doi T, Nagatoshi Y, Fukata M, et al. CD34 + CD38 + CD19+ as well as CD34 + CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL. Leukemia. 2008;22:1207–13.PubMed
90.
Rossi FM, Zucchetto A, Tissino E, Dal Bo M, Bomben R, Caldana C, et al. CD49d expression identifies a chronic-lymphocytic leukemia subset with high levels of mobilized circulating CD34(+) hemopoietic progenitors cells. Leukemia. 2014;28:705–8.PubMed
91.
Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008;68:190–7.PubMedCentralPubMed
92.
Meyer MJ, Fleming JM, Lin AF, Hussnain SA, Ginsburg E, Vonderhaar BK. CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer. Cancer Res. 2010;70:4624–33.PubMedCentralPubMed
93.
Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol. 2013;31:539–44.PubMed
94.
Han ME, Jeon TY, Hwang SH, Lee YS, Kim HJ, Shim HE, et al. Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research. Cell Mol Life Sci. 2011;68:3589–605.PubMed
95.
Fukamachi H, Seol HS, Shimada S, Funasaka C, Baba K, Kim JH, et al. CD49f(high) cells retain sphere-forming and tumor-initiating activities in human gastric tumors. PLoS One. 2013;8:e72438.PubMedCentralPubMed
96.
Jiang J, Zhang Y, Chuai S, Wang Z, Zheng D, Xu F, et al. Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype. Oncogene. 2012;31:671–82.PubMed
97.
Jang BG, Lee BL, Kim WH. Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis. PLoS One. 2013;8:e82390.PubMedCentralPubMed
98.
Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009;27:1006–20.PubMedCentralPubMed
99.
Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104:10158–63.PubMedCentralPubMed
100.
Haraguchi N, Ishii H, Mimori K, Ohta K, Uemura M, Nishimura J, et al. CD49f-positive cell population efficiently enriches colon cancer-initiating cells. Int J Oncol. 2013;43:425–30.PubMed
101.
Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–7.PubMed
102.
Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008;15:504–14.PubMed
103.
Tirino V, Camerlingo R, Franco R, Malanga D, La Rocca A, Viglietto G, et al. The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer. Eur J Cardiothorac Surg. 2009;36(3):446–53.PubMed
104.
Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136:1012–24.PubMedCentralPubMed
105.
Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene. 2008;27:1749–58.PubMed
106.
Kahlert UD, Bender NO, Maciaczyk D, Bogiel T, Bar EE, Eberhart CG, et al. CD133/CD15 defines distinct cell subpopulations with differential in vitro clonogenic activity and stem cell-related gene expression profile in in vitro propagated glioblastoma multiforme-derived cell line with a PNET-like component. Folia Neuropathol. 2012;50:357–68.PubMed
107.
Son MJ, Woolard K, Nam DH, Lee J, Fine HA. SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell. 2009;4:440–52.PubMed
108.
Suva ML, Riggi N, Stehle JC, Baumer K, Tercier S, Joseph JM, et al. Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res. 2009;69:1776–81.PubMed
109.
Tirino V, Desiderio V, Paino F, De Rosa A, Papaccio F, Fazioli F, et al. Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo. Faseb J. 2011;25:2022–30.PubMed
110.
Adhikari AS, Agarwal N, Wood BM, Porretta C, Ruiz B, Pochampally RR, et al. CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance. Cancer Res. 2010;70:4602–12.PubMedCentralPubMed
111.
112.
Meirelles K, Benedict LA, Dombkowski D, Pepin D, Preffer FI, Teixeira J, et al. Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance. Proc Natl Acad Sci U S A. 2012;109:2358–63.PubMedCentralPubMed
113.
Chen J, Wang J, Chen D, Yang J, Yang C, Zhang Y, et al. Evaluation of characteristics of CD44 + CD117+ ovarian cancer stem cells in three dimensional basement membrane extract scaffold versus two dimensional monocultures. BMC Cell Biol. 2013;14:7.PubMedCentralPubMed
114.
Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, et al. CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells. 2009;27:2875–83.PubMed
115.
Guo C, Liu H, Zhang BH, Cadaneanu RM, Mayle AM, Garraway IP. Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability. PLoS One. 2012;7:e34219.PubMedCentralPubMed
116.
Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL. CD44+ CD24(−) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer. 2008;98:756–65.PubMedCentralPubMed
117.
Maitland NJ, Collins AT. Prostate cancer stem cells: a new target for therapy. J Clin Oncol. 2008;26:2862–70.PubMed
118.
Boiko AD, Razorenova OV, van de Rijn M, Swetter SM, Johnson DL, Ly DP, et al. Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature. 2010;466:133–7.PubMedCentralPubMed
119.
Wilson BJ, Saab KR, Ma J, Schatton T, Putz P, Zhan Q, et al. ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit. Cancer Res. 2014;74:4196–207.PubMed
120.
Mirkina I, Hadzijusufovic E, Krepler C, Mikula M, Mechtcheriakova D, Strommer S, et al. Phenotyping of human melanoma cells reveals a unique composition of receptor targets and a subpopulation co-expressing ErbB4, EPO-R and NGF-R. PLoS One. 2014;9:e84417.PubMedCentralPubMed
121.
Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med. 2012;18:618–23.PubMed
122.
Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells. 2012;30:2378–86.PubMed
123.
Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131:1109–23.PubMed
124.
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.PubMedCentralPubMed
125.
Takagi S, Saito Y, Hijikata A, Tanaka S, Watanabe T, Hasegawa T, et al. Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation. Blood. 2012;119:2768–77.PubMedCentralPubMed
126.
Sarry JE, Murphy K, Perry R, Sanchez PV, Secreto A, Keefer C, et al. Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rgammac-deficient mice. J Clin Invest. 2011;121:384–95.PubMedCentralPubMed
127.
Vercauteren SM, Sutherland HJ. CD133 (AC133) expression on AML cells and progenitors. Cytotherapy. 2001;3:449–59.PubMed
128.
Valent P, Bonnet D, Wohrer S, Andreeff M, Copland M, Chomienne C, et al. Heterogeneity of Neoplastic Stem Cells: Theoretical, Functional, and Clinical Implications. Cancer Res. 2013;73:1037–45.PubMed
129.
Chaffer CL, Brueckmann I, Scheel C, Kaestli AJ, Wiggins PA, Rodrigues LO, et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci U S A. 2011;108:7950–5.PubMedCentralPubMed
130.
Valent P, Bonnet D, De Maria R, Lapidot T, Copland M, Melo JV, et al. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer. 2012;12:767–75.PubMed
131.
Jan M, Snyder TM, Corces-Zimmerman MR, Vyas P, Weissman IL, Quake SR, et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci Transl Med. 2012;4:149ra118.PubMedCentralPubMed
132.
Valent P, Lion T, Wolf D, Sillaber C, Agis H, Petzer A, et al. Diagnostic algorithms, monitoring, prognostication, and therapy in chronic myeloid leukemia (CML): a proposal of the Austrian CML platform. Wien Klin Wochenschr. 2008;120:697–709.PubMed
133.
Renström J, Kröger M, Peschel C, Oostendorp RAJ. How the niche regulates hematopoietic stem cells. Chem Biol Interact. 2010;184:7–15.PubMed
134.
Wang P, Hou SX. Regulation of intestinal stem cells in mammals and Drosophila. J Cell Physiol. 2009;222:33–7.
135.
Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12:133–43.PubMed
136.
Niebuhr B, Fischer M, Tager M, Cammenga J, Stocking C. Gatekeeper function of the RUNX1 transcription factor in acute leukemia. Blood Cells Mol Dis. 2008;40:211–8.PubMed
137.
Wang X, Tripodi J, Kremyanskaya M, Blouin A, Roda P, Hoffman R, et al. BCR-ABL1 is a secondary event after JAK2V617F in patients with polycythemia vera who develop chronic myeloid leukemia. Blood. 2013;121:1238–9.PubMed
138.
Itzykson R, Solary E. An evolutionary perspective on chronic myelomonocytic leukemia. Leukemia. 2013;27:1441–50.PubMed
139.
Herrmann H. Phenotypic and functional characterization of CD34+/CD38−/CD123+ leukemic progenitor (stem) cells in AML: a flow cytometric approach. In: 50th ASH Annual Meeting and Exposition. 2008.
140.
Morimoto K, Kim SJ, Tanei T, Shimazu K, Tanji Y, Taguchi T, et al. Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression. Cancer Sci. 2009;100:1062–8.PubMed
141.
Korkaya H, Paulson A, Iovino F, Wicha MS. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene. 2008;27:6120–30.PubMedCentralPubMed
142.
Hewish M, Chau I, Cunningham D. Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. Recent Patents Anticancer Drug Discov. 2009;4:54–72.
143.
Gotoh N. Control of stemness by fibroblast growth factor signaling in stem cells and cancer stem cells. Curr Stem Cell Res Ther. 2009;4:9–15.PubMed
144.
Koneczny I, Schulenburg A, Hudec X, Knofler M, Holzmann K, Piazza G, et al. Autocrine fibroblast growth factor 18 signaling mediates Wnt-dependent stimulation of CD44-positive human colorectal adenoma cells. Mol Carcinog. 2014. doi:10.1002/mc.22146.
145.
Jiang X, Lopez A, Holyoake T, Eaves A, Eaves C. Autocrine production and action of IL-3 and granulocyte colony-stimulating factor in chronic myeloid leukemia. Proc Natl Acad Sci U S A. 1999;96:12804–9.PubMedCentralPubMed
146.
Jiang X, Fujisaki T, Nicolini F, Berger M, Holyoake T, Eisterer W, et al. Autonomous multi-lineage differentiation in vitro of primitive CD34+ cells from patients with chronic myeloid leukemia. Leukemia. 2000;14:1112–21.PubMed
147.
Zhang SS, Han ZP, Jing YY, Tao SF, Li TJ, Wang H, et al. CD133(+)CXCR4(+) colon cancer cells exhibit metastatic potential and predict poor prognosis of patients. BMC Med. 2012;10:85.PubMedCentralPubMed
148.
Furusato B, Mohamed A, Uhlen M, Rhim JS. CXCR4 and cancer. Pathol Int. 2010;60:497–505.PubMed
149.
Tavor S, Petit I. Can inhibition of the SDF-1/CXCR4 axis eradicate acute leukemia? Semin Cancer Biol. 2010;20:178–85.PubMed
150.
Tavor S, Petit I, Porozov S, Avigdor A, Dar A, Leider-Trejo L, et al. CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Res. 2004;64:2817–24.PubMed
151.
Kumar SM, Zhang G, Bastian BC, Arcasoy MO, Karande P, Pushparajan A, et al. Erythropoietin receptor contributes to melanoma cell survival in vivo. Oncogene. 2012;31:1649–60.PubMedCentralPubMed
152.
Sinclair AM, Todd MD, Forsythe K, Knox SJ, Elliott S, Begley CG. Expression and function of erythropoietin receptors in tumors: implications for the use of erythropoiesis-stimulating agents in cancer patients. Cancer. 2007;110:477–88.PubMed
153.
Jelkmann W, Bohlius J, Hallek M, Sytkowski AJ. The erythropoietin receptor in normal and cancer tissues. Crit Rev Oncol Hematol. 2008;67:39–61.PubMed
154.
Gonen M, Sun Z, Figueroa ME, Patel JP, Abdel-Wahab O, Racevskis J, et al. CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900. Blood. 2012;120:2297–306.PubMedCentralPubMed
155.
Testa U, Riccioni R, Diverio D, Rossini A, Lo Coco F, Peschle C. Interleukin-3 receptor in acute leukemia. Leukemia. 2004;18:219–26.PubMed
156.
Lowenberg B, van Putten W, Theobald M, Gmur J, Verdonck L, Sonneveld P, et al. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003;349:743–52.PubMed
157.
Frohling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002;100:4372–80.PubMed
158.
Hassan HT, Zander A. Stem cell factor as a survival and growth factor in human normal and malignant hematopoiesis. Acta Haematol. 1996;95:257–62.PubMed
159.
Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM, et al. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. 2012;119:3917–24.PubMedCentralPubMed
160.
Hanumanthu VS, Pirruccello SJ. GCSF-R expression in myelodysplastic and myeloproliferative disorders and blast dysmaturation in CML. Am J Clin Pathol. 2013;140:155–64.PubMed
161.
Zhang Y, Guo Q, Zhao H, Zhao D, Wu X, Zhao W, et al. Expression of CXCR4 is an independent prognostic factor for overall survival and progression-free survival in patients with myelodysplastic syndrome. Med Oncol. 2013;30:341.PubMed
162.
Nakata Y, Kimura A, Katoh O, Kawaishi K, Hyodo H, Abe K, et al. c-kit point mutation of extracellular domain in patients with myeloproliferative disorders. Br J Haematol. 1995;91:661–3.PubMed
163.
Bogani C, Ponziani V, Guglielmelli P, Desterke C, Rosti V, Bosi A, et al. Hypermethylation of CXCR4 promoter in CD34+ cells from patients with primary myelofibrosis. Stem Cells. 2008;26:1920–30.PubMed
164.
Smith BD, Kasamon YL, Kowalski J, Gocke C, Murphy K, Miller CB, et al. K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res. 2010;16:338–47.PubMedCentralPubMed
165.
Corbin AS, O’Hare T, Gu Z, Kraft IL, Eiring AM, Khorashad JS, et al. KIT signaling governs differential sensitivity of mature and primitive CML progenitors to tyrosine kinase inhibitors. Cancer Res. 2013;73:5775–86.PubMedCentralPubMed
166.
Beider K, Darash-Yahana M, Blaier O, Koren-Michowitz M, Abraham M, Wald H, et al. Combination of imatinib with CXCR4 antagonist BKT140 overcomes the protective effect of stroma and targets CML in vitro and in vivo. Mol Cancer Ther. 2014;13:1155–69.PubMed
167.
Gaikwad AS, Donohue RE, Elghetany MT, Sheehan AM, Lu XY, Gramatges MM, et al. Expression of CD25 is a specific and relatively sensitive marker for the Philadelphia chromosome (BCR-ABL1) translocation in pediatric B acute lymphoblastic leukemia. Int J Clin Exp Pathol. 2014;7:6225–30.PubMedCentralPubMed
168.
Kim HP, Frankel AE, Hogge DE. A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia. Leuk Res. 2010;34:1035–42.PubMed
169.
Parameswaran R, Yu M, Lim M, Groffen J, Heisterkamp N. Combination of drug therapy in acute lymphoblastic leukemia with a CXCR4 antagonist. Leukemia. 2011;25:1314–23.PubMedCentralPubMed
170.
Peled A, Abraham M, Avivi I, Rowe JM, Beider K, Wald H, et al. The high-affinity CXCR4 antagonist BKT140 is safe and induces a robust mobilization of human CD34+ cells in patients with multiple myeloma. Clin Cancer Res. 2014;20:469–79.PubMed
171.
LeBedis C, Chen K, Fallavollita L, Boutros T, Brodt P. Peripheral lymph node stromal cells can promote growth and tumorigenicity of breast carcinoma cells through the release of IGF-I and EGF. Int J Cancer. 2002;100:2–8.PubMed
172.
Korkaya H, Wicha MS. HER2 and breast cancer stem cells: more than meets the eye. Cancer Res. 2013;73:3489–93.PubMed
173.
Fillmore CM, Gupta PB, Rudnick JA, Caballero S, Keller PJ, Lander ES, et al. Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci U S A. 2010;107:21737–42.PubMedCentralPubMed
174.
Sun L, Wu G, Willson JK, Zborowska E, Yang J, Rajkarunanayake I, et al. Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem. 1994;269:26449–55.PubMed
175.
Pinto C, Di Fabio F, Siena S, Cascinu S, Rojas Llimpe FL, Ceccarelli C, et al. Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol. 2007;18:510–7.PubMed
176.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.PubMed
177.
Shaib W, Mahajan R, El-Rayes B. Markers of resistance to anti-EGFR therapy in colorectal cancer. J Gastrointest Oncol. 2013;4:308–18.PubMedCentralPubMed
178.
Kim J, Takeuchi H, Lam ST, Turner RR, Wang HJ, Kuo C, et al. Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol. 2005;23:2744–53.PubMed
179.
Wolpin BM, Meyerhardt JA, Chan AT, Ng K, Chan JA, Wu K, et al. Insulin, the insulin-like growth factor axis, and mortality in patients with nonmetastatic colorectal cancer. J Clin Oncol. 2009;27:176–85.PubMedCentralPubMed
180.
Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Cespedes MV, et al. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012;22:571–84.PubMedCentralPubMed
181.
Okamoto I, Araki J, Suto R, Shimada M, Nakagawa K, Fukuoka M. EGFR mutation in gefitinib-responsive small-cell lung cancer. Ann Oncol. 2006;17:1028–9.PubMed
182.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.PubMed
183.
Shan J, Shen J, Liu L, Xia F, Xu C, Duan G, et al. Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology. 2012;56:1004–14.PubMed
184.
Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985;313:144–7.PubMed
185.
Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, et al. Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res. 1992;52:3213–9.PubMed
186.
Ehtesham M, Mapara KY, Stevenson CB, Thompson RC. CXCR4 mediates the proliferation of glioblastoma progenitor cells. Cancer Lett. 2009;274:305–12.PubMedCentralPubMed
187.
Penuelas S, Anido J, Prieto-Sanchez RM, Folch G, Barba I, Cuartas I, et al. TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Cancer Cell. 2009;15:315–27.PubMed
188.
Joo KM, Jin J, Kim E, Ho Kim K, Kim Y, Gu Kang B, et al. MET signaling regulates glioblastoma stem cells. Cancer Res. 2012;72:3828–38.PubMed
189.
Glaysher S, Bolton LM, Johnson P, Atkey N, Dyson M, Torrance C, et al. Targeting EGFR and PI3K pathways in ovarian cancer. Br J Cancer. 2013;109:1786–94.PubMedCentralPubMed
190.
Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol. 2003;21:283–90.PubMed
191.
Yeung TL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, et al. TGF-beta modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 2013;73:5016–28.PubMedCentralPubMed
192.
Dubrovska A, Elliott J, Salamone RJ, Telegeev GD, Stakhovsky AE, Schepotin IB, et al. CXCR4 expression in prostate cancer progenitor cells. PLoS One. 2012;7:e31226.PubMedCentralPubMed
193.
Singh S, Nannuru KC, Sadanandam A, Varney ML, Singh RK. CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion. Br J Cancer. 2009;100:1638–46.PubMedCentralPubMed
194.
Karamboulas C, Ailles L. Developmental signaling pathways in cancer stem cells of solid tumors. Biochim Biophys Acta. 1830;2013:2481–95.
195.
Okuhashi Y, Itoh M, Nara N, Tohda S. Effects of combination of Notch inhibitor plus hedgehog inhibitor or Wnt inhibitor on growth of leukemia cells. Anticancer Res. 2011;31:893–6.PubMed
196.
Sinclair A, Latif AL, Holyoake TL. Targeting survival pathways in chronic myeloid leukaemia stem cells. Br J Pharmacol. 2013;169:1693–707.PubMedCentralPubMed
197.
Abetov D, Mustapova Z, Saliev T, Bulanin D. Biomarkers and signaling pathways of colorectal cancer stem cells. Tumour Biol. 2015;doi:10.1007/s13277-015-3198-4.
198.
Takahashi-Yanaga F, Kahn M. Targeting Wnt signaling: can we safely eradicate cancer stem cells? Clin Cancer Res. 2010;16:3153–62.PubMed
199.
Dey A, Seshasayee D, Noubade R, French DM, Liu J, Chaurushiya MS, et al. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science. 2012;337:1541–6.PubMed
200.
Kleppe M, Levine RL. Targeting beta-catenin in CML: leukemia stem cells beware! Cell Stem Cell. 2012;10:351–3.PubMed
201.
Pannuti A, Foreman K, Rizzo P, Osipo C, Golde T, Osborne B, et al. Targeting Notch to target cancer stem cells. Clin Cancer Res. 2010;16:3141–52.PubMedCentralPubMed
202.
203.
Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561–6.PubMed
204.
Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest. 2011;121:396–409.PubMedCentralPubMed
205.
Hamilton A, Elrick L, Myssina S, Copland M, Jorgensen H, Melo JV, et al. BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry. Leukemia. 2006;20:1035–9.PubMed
206.
Wiseman DH, Greystoke BF, Somervaille TC. The variety of leukemic stem cells in myeloid malignancy. Oncogene. 2013;33(24):3091–8.PubMed
207.
Anderson K, Lutz C, van Delft FW, Bateman CM, Guo Y, Colman SM, et al. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature. 2011;469:356–61.PubMed
208.
Ysebaert L, Chicanne G, Demur C, De Toni F, Prade-Houdellier N, Ruidavets JB, et al. Expression of beta-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia. 2006;20:1211–6.PubMed
209.
Li Y, Welm B, Podsypanina K, Huang SX, Chamorro M, Zhang XM, et al. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci U S A. 2003;100:15853–8.PubMedCentralPubMed
210.
Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, et al. Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc Natl Acad Sci U S A. 2009;106:1193–8.PubMedCentralPubMed
211.
Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, et al. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res. 2008;68:4287–95.PubMed
212.
Gursel DB, Berry N, Boockvar JA. The contribution of Notch signaling to glioblastoma via activation of cancer stem cell self-renewal: the role of the endothelial network. Neurosurgery. 2012;70:N19–21.PubMed
213.
Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, et al. NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res. 2010;70:1469–78.PubMedCentralPubMed
214.
Lee CW, Simin K, Liu Q, Plescia J, Guha M, Khan A, et al. A functional Notch-survivin gene signature in basal breast cancer. Breast Cancer Res. 2008;10:R97.PubMedCentralPubMed
215.
Liu SL, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006;66:6063–71.PubMed
216.
Huang FT, Zhuan-Sun YX, Zhuang YY, Wei SL, Tang J, Chen WB, et al. Inhibition of Hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance. J Gastroen Hepatol. 2012;27:43.
217.
Kawaguchi-Ihara N, Okuhashi Y, Itoh M, Murohashi I, Nara N, Tohda S. Promotion of the self-renewal capacity of human leukemia cells by sonic hedgehog protein. Anticancer Res. 2011;31:781–4.PubMed
218.
Ferruzzi P, Mennillo F, De Rosa A, Giordano C, Rossi M, Benedetti G, et al. In vitro and in vivo characterization of a novel hedgehog signaling antagonist in human glioblastoma cell lines. Int J Cancer. 2012;131:E33–44.PubMed
219.
Mazumdar T, DeVecchio J, Shi T, Jones J, Agyeman A, Houghton JA. Hedgehog signaling drives cellular survival in human colon carcinoma cells. Cancer Res. 2011;71:1092–102.PubMedCentralPubMed
220.
Phelps RA, Chidester S, Dehghanizadeh S, Phelps J, Sandoval IT, Rai K, et al. A two-step model for colon adenoma initiation and progression caused by APC loss. Cell. 2009;137:623–34.PubMedCentralPubMed
221.
Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, et al. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol. 2009;7:e1000121.PubMedCentralPubMed
222.
Kroon P, Berry PA, Stower MJ, Rodrigues G, Mann VM, Simms M, et al. JAK-STAT blockade inhibits tumor initiation and clonogenic recovery of prostate cancer stem-like cells. Cancer Res. 2013;73:5288–98.PubMed
223.
Kanno H, Sato H, Yokoyama T-A, Yoshizumi T, Yamada S. The VHL tumor suppressor protein regulates tumorigenicity of U87-derived glioma stem-like cells by inhibiting the JAK/STAT signaling pathway. Int J Oncol. 2013;42:881–6.PubMed
224.
Krause DS, Lazarides K, von Andrian UH, Van Etten RA. Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat Med. 2006;12:1175–80.PubMed
225.
Nair RR, Tolentino J, Hazlehurst LA. The bone marrow microenvironment as a sanctuary for minimal residual disease in CML. Biochem Pharmacol. 2010;80:602–12.PubMedCentralPubMed
226.
Potten CS, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990;110:1001–20.PubMed
227.
Jones DL, Wagers AJ. No place like home: anatomy and function of the stem cell niche. Nat Rev Mol Cell Biol. 2008;9:11–21.PubMed
228.
Rosel M, Khaldoyanidi S, Zawadzki V, Zoller M. Involvement of CD44 variant isoform v10 in progenitor cell adhesion and maturation. Exp Hematol. 1999;27:698–711.PubMed
229.
Alakel N, Jing D, Muller K, Bornhauser M, Ehninger G, Ordemann R. Direct contact with mesenchymal stromal cells affects migratory behavior and gene expression profile of CD133(+) hematopoietic stem cells during ex vivo expansion. Exp Hematol. 2009;37(4):504–13.PubMed
230.
Raveh S, Gavert N, Ben-Ze'ev A. L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer Lett. 2009;282(2):137–45.PubMed
231.
Gavert N, Ben-Shmuel A, Raveh S, Ben-Ze’ev A. L1-CAM in cancerous tissues. Expert Opin Biol Ther. 2008;8:1749–57.PubMed
232.
Bao S, Wu Q, Li Z, Sathornsumetee S, Wang H, McLendon RE, et al. Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res. 2008;68:6043–8.PubMedCentralPubMed
233.
Kang Y, Massague J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 2004;118:277–9.PubMed
234.
Peled A, Hardan I, Trakhtenbrot L, Gur E, Magid M, Darash-Yahana M, et al. Immature leukemic CD34(+)CXCR4(+) cells from CML patients have lower integrin-dependent migration and adhesion in response to the chemokine SDF-1. Stem Cells. 2002;20:259–66.PubMed
235.
Zhang B, Ho YW, Huang Q, Maeda T, Lin A, Lee SU, et al. Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia. Cancer Cell. 2012;21:577–92.PubMedCentralPubMed
236.
Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441:1075–9.PubMed
237.
Greenberger JS. The hematopoietic microenvironment. Crit Rev Oncol Hematol. 1991;11:65–84.PubMed
238.
239.
Mayani H, Guilbert LJ, Janowska-Wieczorek A. Biology of the hemopoietic microenvironment. Eur J Haematol. 1992;49:225–33.PubMed
240.
Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994;76:301–14.PubMed
241.
Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.PubMed
242.
Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA. Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. Blood. 1996;88:146–57.PubMed
243.
Schulenburg A, Cech P, Herbacek I, Marian B, Wrba F, Valent P, et al. CD44-positive colorectal adenoma cells express the potential stem cell markers musashi antigen (msi1) and ephrin B2 receptor (EphB2). J Pathol. 2007;213:152–60.PubMed
244.
De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013;13:97–110.PubMed
245.
Savagner P. The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol. 2010;21 Suppl 7:vii89-92.PubMed
246.
Durig J, Rosenthal C, Elmaagacli A, Heyworth C, Halfmeyer K, Kasper C, et al. Biological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells. Leukemia. 2000;14:1652–60.PubMed
247.
Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013;502:637–43.PubMed
248.
Scadden DT. Nice neighborhood: emerging concepts of the stem cell niche. Cell. 2014;157:41–50.PubMed
249.
Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505:327–34.PubMed
250.
Konopleva M, Tabe Y, Zeng Z, Andreeff M. Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches. Drug Resist Updat. 2009;12:103–13.PubMedCentralPubMed
251.
Sullivan WJ, Christofk HR. The metabolic milieu of metastases. Cell. 2015;160:363–4.PubMed
252.
Xiang L, Gilkes DM, Hu H, Takano N, Luo W, Lu H, et al. Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to induce the breast cancer stem cell phenotype. Oncotarget. 2014;5:12509–27.PubMed
253.
Clarke L, van der Kooy D. Low oxygen enhances primitive and definitive neural stem cell colony formation by inhibiting distinct cell death pathways. Stem Cells. 2009;27:1879–86.PubMedCentralPubMed
254.
Moreno-Manzano V, Rodriguez-Jimenez FJ, Acena-Bonilla JL, Fustero-Lardies S, Erceg S, Dopazo J, et al. FM19G11, a new hypoxia-inducible factor (HIF) modulator, affects stem cell differentiation status. J Biol Chem. 2010;285:1333–42.PubMedCentralPubMed
255.
Levesque JP, Winkler IG, Hendy J, Williams B, Helwani F, Barbier V, et al. Hematopoietic progenitor cell mobilization results in hypoxia with increased hypoxia-inducible transcription factor-1 alpha and vascular endothelial growth factor A in bone marrow. Stem Cells. 2007;25:1954–65.PubMed
256.
Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10:858–64.PubMed
257.
Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, et al. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 2005;9:617–28.PubMed
258.
Chen Y, De Marco MA, Graziani I, Gazdar AF, Strack PR, Miele L, et al. Oxygen concentration determines the biological effects of NOTCH-1 signaling in adenocarcinoma of the lung. Cancer Res. 2007;67:7954–9.PubMed
259.
Gilbertson RJ, Rich JN. Making a tumour’s bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer. 2007;7:733–6.PubMed
260.
Nieborowska-Skorska M, Kopinski PK, Ray R, Hoser G, Ngaba D, Flis S, et al. Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors. Blood. 2012;119:4253–63.PubMedCentralPubMed
261.
Kantner HP, Warsch W, Delogu A, Bauer E, Esterbauer H, Casanova E, et al. ETV6/RUNX1 induces reactive oxygen species and drives the accumulation of DNA damage in B cells. Neoplasia. 2013;15:1292–300.PubMedCentralPubMed
262.
Warsch W, Grundschober E, Berger A, Gille L, Cerny-Reiterer S, Tigan AS, et al. STAT5 triggers BCR-ABL1 mutation by mediating ROS production in chronic myeloid leukaemia. Oncotarget. 2012;3:1669–87.PubMedCentralPubMed
263.
Covello KL, Kehler J, Yu H, Gordan JD, Arsham AM, Hu CJ, et al. HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 2006;20:557–70.PubMedCentralPubMed
264.
265.
266.
Oh SH, Park TS, Kim HR, Lee JY, Kim JH, Shin JH, et al. Chronic myelogenous leukemia showing biphenotypic blast crisis followed by lineage switch to B lymphoblastic leukemia. Leuk Res. 2009;33:e195–8.PubMed
267.
Schmidt CA, Przybylski GK. What can we learn from leukemia as for the process of lineage commitment in hematopoiesis? Int Rev Immunol. 2001;20:107–15.PubMed
268.
Reid AG, De Melo VA, Elderfield K, Clark I, Marin D, Apperley J, et al. Phenotype of blasts in chronic myeloid leukemia in blastic phase-analysis of bone marrow trephine biopsies and correlation with cytogenetics. Leuk Res. 2009;33:418–25.PubMed
269.
Bettelheim P, Lutz D, Majdic O, Paietta E, Haas O, Linkesch W, et al. Cell lineage heterogeneity in blast crisis of chronic myeloid leukaemia. Br J Haematol. 1985;59:395–409.PubMed
270.
Goradia A, Bayerl M, Cornfield D. The 8p11 myeloproliferative syndrome: review of literature and an illustrative case report. Int J Clin Exp Pathol. 2008;1:448–56.PubMedCentralPubMed
271.
Tzankov A, Sotlar K, Muhlematter D, Theocharides A, Went P, Jotterand M, et al. Systemic mastocytosis with associated myeloproliferative disease and precursor B lymphoblastic leukaemia with t(13;13)(q12;q22) involving FLT3. J Clin Pathol. 2008;61:958–61.PubMed
272.
Sperr WR, Horny HP, Valent P. Spectrum of associated clonal hematologic non-mast cell lineage disorders occurring in patients with systemic mastocytosis. Int Arch Allergy Immunol. 2002;127:140–2.PubMed
273.
Streubel B, Chott A, Huber D, Exner M, Jager U, Wagner O, et al. Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas. N Engl J Med. 2004;351:250–9.PubMed
274.
Gunsilius E, Duba HC, Petzer AL, Kahler CM, Grunewald K, Stockhammer G, et al. Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Lancet. 2000;355:1688–91.PubMed
275.
Wu J, Huang L, Huang M, Liu W, Zheng M, Cao Y, et al. Dominant contribution of malignant endothelial cells to endotheliopoiesis in chronic myeloid leukemia. Exp Hematol. 2009;37:87–91.PubMed
276.
Mirshahi P, Rafii A, Vincent L, Berthaut A, Varin R, Kalantar G, et al. Vasculogenic mimicry of acute leukemic bone marrow stromal cells. Leukemia. 2009;23:1039–48.PubMed
277.
Hauswirth AW, Florian S, Printz D, Sotlar K, Krauth MT, Fritsch G, et al. Expression of the target receptor CD33 in CD34+/CD38-/CD123+ AML stem cells. Eur J Clin Invest. 2007;37:73–82.PubMed
278.
Pearce DJ, Taussig DC, Bonnet D. Implications of the expression of myeloid markers on normal and leukemic stem cells. Cell Cycle. 2006;5:271–3.PubMed
279.
Larson RA, Boogaerts M, Estey E, Karanes C, Stadtmauer EA, Sievers EL, et al. Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia. 2002;16:1627–36.PubMed
280.
Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001;19:3244–54.PubMed
281.
Feldman E, Kalaycio M, Weiner G, Frankel S, Schulman P, Schwartzberg L, et al. Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195. Leukemia. 2003;17:314–8.PubMed
282.
Sievers EL, Appelbaum FR, Spielberger RT, Forman SJ, Flowers D, Smith FO, et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood. 1999;93:3678–84.PubMed
283.
Majeti R. Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells. Oncogene. 2011;30:1009–19.PubMed
284.
Mahon F-X, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11:1029–35.PubMed
285.
Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9:105–16.PubMed
286.
Patz M, Isaeva P, Forcob N, Muller B, Frenzel LP, Wendtner CM, et al. Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells. Br J Haematol. 2011;152:295–306.PubMed
287.
Boyd K, Dearden CE. Alemtuzumab in the treatment of chronic lymphocytic lymphoma. Expert Rev Anticancer Ther. 2008;8:525–33.PubMed
288.
Cunningham MP, Thomas H, Marks C, Green M, Fan Z, Modjtahedi H. Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells. Int J Oncol. 2008;33:1107–13.PubMed
289.
Heinrich MC. Imatinib treatment of metastatic GIST: don’t stop (believing). Lancet Oncol. 2010;11:910–1.PubMed
290.
Burris 3rd HA, Hurwitz HI, Dees EC, Dowlati A, Blackwell KL, O’Neil B, et al. Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol. 2005;23:5305–13.PubMed
291.
Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366:2171–9.PubMed
292.
Ribas A, Flaherty KT. BRAF targeted therapy changes the treatment paradigm in melanoma. Nat Rev Clin Oncol. 2011;8:426–33.PubMed
293.
Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32–42.PubMedCentralPubMed
294.
Galanis E, Buckner JC, Maurer MJ, Kreisberg JI, Ballman K, Boni J, et al. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J Clin Oncol. 2005;23:5294–304.PubMed
295.
Hudes GR. mTOR as a target for therapy of renal cancer. Clin Adv Hematol Oncol. 2007;5:772–4.PubMed
296.
Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478:524–8.PubMedCentralPubMed
297.
Fons P, Herault JP, Delesque N, Tuyaret J, Bono F, Herbert JM. VEGF-R2 and neuropilin-1 are involved in VEGF-A-induced differentiation of human bone marrow progenitor cells. J Cell Physiol. 2004;200:351–9.PubMed
298.
Shervington A, Lu C. Expression of multidrug resistance genes in normal and cancer stem cells. Cancer Invest. 2008;26:535–42.PubMed
299.
Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002;53:615–27.PubMed
300.
Engler JR, Frede A, Saunders V, Zannettino A, White DL, Hughes TP. The poor response to imatinib observed in CML patients with low OCT-1 activity is not attributable to lower uptake of imatinib into their CD34+ cells. Blood. 2010;116:2776–8.PubMed
301.
Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res. 2005;65:6207–19.PubMed
302.
Nakai E, Park K, Yawata T, Chihara T, Kumazawa A, Nakabayashi H, et al. Enhanced MDR1 expression and chemoresistance of cancer stem cells derived from glioblastoma. Cancer Invest. 2009;27:901–8.PubMed
303.
Yamamoto A, Shofuda T, Islam MO, Nakamura Y, Yamasaki M, Okano H, et al. ABCB1 is predominantly expressed in human fetal neural stem/progenitor cells at an early development stage. J Neurosci Res. 2009;87:2615–23.PubMed
304.
Jin W, Liu Y, Xu SG, Yin WJ, Li JJ, Yang JM, et al. UHRF1 inhibits MDR1 gene transcription and sensitizes breast cancer cells to anticancer drugs. Breast Cancer Res Treat. 2010;124:39–48.PubMed
305.
Brendel C, Scharenberg C, Dohse M, Robey RW, Bates SE, Shukla S, et al. Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells. Leukemia. 2007;21:1267–75.PubMed
306.
Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, et al. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood. 2001;98:2301–7.PubMed
307.
Zhang J, Grindley JC, Yin T, Jayasinghe S, He XC, Ross JT, et al. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature. 2006;441:518–22.PubMed
308.
Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441:475–82.PubMed
309.
Hess CJ, Berkhof J, Denkers F, Ossenkoppele GJ, Schouten JP, Oudejans JJ, et al. Activated intrinsic apoptosis pathway is a key related prognostic parameter in acute myeloid leukemia. J Clin Oncol. 2007;25:1209–15.PubMed
310.
Harper LJ, Costea DE, Gammon L, Fazil B, Biddle A, Mackenzie IC. Normal and malignant epithelial cells with stem-like properties have an extended G2 cell cycle phase that is associated with apoptotic resistance. BMC Cancer. 2010;10:166.PubMedCentralPubMed
311.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.PubMed
312.
Skladanowski A, Bozko P, Sabisz M. DNA structure and integrity checkpoints during the cell cycle and their role in drug targeting and sensitivity of tumor cells to anticancer treatment. Chem Rev. 2009;109:2951–73.PubMed
313.
Lane SW, Scadden DT, Gilliland DG. The leukemic stem cell niche: current concepts and therapeutic opportunities. Blood. 2009;114:1150–7.PubMedCentralPubMed
314.
Teitz-Tennenbaum S, Wicha MS, Chang AE, Li Q. Targeting cancer stem cells via dendritic-cell vaccination. Oncoimmunology. 2012;1:1401–3.PubMedCentralPubMed
315.
Brune M, Castaigne S, Catalano J, Gehlsen K, Ho AD, Hofmann WK, et al. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial. Blood. 2006;108:88–96.PubMed
316.
Essers MA, Trumpp A. Targeting leukemic stem cells by breaking their dormancy. Mol Oncol. 2010;4:443–50.PubMed
317.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.PubMedCentralPubMed
318.
Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24:207–12.PubMedCentralPubMed
319.
Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–42.PubMed
320.
Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, et al. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006;66:7843–8.PubMed
321.
Wulf GG, Wang RY, Kuehnle I, Weidner D, Marini F, Brenner MK, et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood. 2001;98:1166–73.PubMed
322.
Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci U S A. 2004;101:14228–33.PubMedCentralPubMed
323.
Peter B, Cerny-Reiterer S, Hadzijusufovic E, Schuch K, Stefanzl G, Eisenwort G, et al. The pan-Bcl-2 blocker obatoclax promotes the expression of Puma, Noxa, and Bim mRNA and induces apoptosis in neoplastic mast cells. J Leukoc Biol. 2014;95:95–104.PubMed
324.
Moser C, Lang SA, Kainz S, Gaumann A, Fichtner-Feigl S, Koehl GE, et al. Blocking heat shock protein-90 inhibits the invasive properties and hepatic growth of human colon cancer cells and improves the efficacy of oxaliplatin in p53-deficient colon cancer tumors in vivo. Mol Cancer Ther. 2007;6:2868–78.PubMed
325.
Clappier E, Gerby B, Sigaux F, Delord M, Touzri F, Hernandez L, et al. Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse. J Exp Med. 2011;208:653–61.PubMedCentralPubMed
326.
Hochhaus A. Chronic myelogenous leukemia (CML): resistance to tyrosine kinase inhibitors. Ann Oncol. 2006;17 Suppl 10:x274–9.PubMed
327.
Druker BJ. Translation of the Philadelphia chromosome into therapy for CML. Blood. 2008;112:4808–17.PubMed
328.
Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876–80.PubMed
329.
Carter TA, Wodicka LM, Shah NP, Velasco AM, Fabian MA, Treiber DK, et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci U S A. 2005;102:11011–6.PubMedCentralPubMed
330.
Deininger M. Resistance and relapse with imatinib in CML: causes and consequences. J Natl Compr Canc Netw. 2008;6 Suppl 2:S11–21.PubMed
331.
Quintas-Cardama A, Kantarjian HM, Cortes JE. Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control. 2009;16:122–31.PubMed
332.
Andreeff M, Konopleva M. Mechanisms of drug resistance in AML. Cancer Treat Res. 2002;112:237–62.PubMed
333.
Thomas X, Campos L, Le QH, Guyotat D. Heat shock proteins and acute leukemias. Hematology. 2005;10:225–35.PubMed
334.
Haase D, Germing U, Schanz J, Pfeilstocker M, Nosslinger T, Hildebrandt B, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110:4385–95.PubMed
335.
Mrozek K. Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype. Semin Oncol. 2008;35:365–77.PubMedCentralPubMed
336.
Cortes JE, Talpaz M, Giles F, O’Brien S, Rios MB, Shan J, et al. Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood. 2003;101:3794–800.PubMed
337.
Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84.PubMed
338.
Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367:2075–88.PubMedCentralPubMed
339.
Blay JY. A decade of tyrosine kinase inhibitor therapy: historical and current perspectives on targeted therapy for GIST. Cancer Treat Rev. 2011;37:373–84.PubMed
340.
Kanda T, Ishikawa T, Takahashi T, Nishida T. Nilotinib for treatment of gastrointestinal stromal tumors: out of the equation? Expert Opin Pharmacother. 2013;14:1859–67.PubMed
341.
Iorio N, Sawaya RA, Friedenberg FK. Review article: the biology, diagnosis and management of gastrointestinal stromal tumours. Aliment Pharmacol Ther. 2014;39(12):1376–86.PubMed
342.
Shoji S, Nakano M, Sato H, Tang XY, Osamura YR, Terachi T, et al. The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma. Clin Exp Metastasis. 2014;31:111–34.PubMed
343.
Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369:722–31.PubMed
344.
Plosker GL, Figgitt DP. Rituximab: a review of its use in non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs. 2003;63:803–43.PubMed
345.
Cheson BD, Leonard JP. Monoclonal antibody therapy for B-cell non-Hodgkin’s lymphoma. N Engl J Med. 2008;359:613–26.PubMed
346.
Agarwal A, Fleischman AG, Petersen CL, MacKenzie R, Luty S, Loriaux M, et al. Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML. Blood. 2012;120:2658–68.PubMedCentralPubMed
347.
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.PubMed
348.
Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, et al. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood. 2012;119:3403–12.PubMed
349.
Damon LE. Mobilization of hematopoietic stem cells into the peripheral blood. Expert Rev Hematol. 2009;2:717–33.PubMed
350.
Uy GL, Rettig MP, Cashen AF. Plerixafor, a CXCR4 antagonist for the mobilization of hematopoietic stem cells. Expert Opin Biol Ther. 2008;8:1797–804.PubMed
351.
Hadzijusufovic E, Herndlhofer S, Aichberger KJ, Ghanim V, Suppan V, Cerny-Reiterer S, et al. Nilotinib exerts direct effects on vascular endothelial cells and may act as a co-trigger of atherosclerosis in patients with Ph plus CML. Blood. 2011;118:1183–4.
352.
353.
Hamilton A, Helgason GV, Schemionek M, Zhang B, Myssina S, Allan EK, et al. Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood. 2012;119:1501–10.PubMedCentralPubMed
Metadata
Title
Cancer stem cells in basic science and in translational oncology: can we translate into clinical application?
Publication date
01-12-2015
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0113-9

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