Chronic myeloid leukemia stem cells in the era of targeted therapies: resistance, persistence and long-term dormancy

Melo, 2003, Chronic myeloid leukemia--advances in biology and new approaches to treatment, N Engl J Med, 349, 1451, 10.1056/NEJMra020777

Skorski, 2007, Genomic instability: The cause and effect of BCR/ABL tyrosine kinase, Curr Hematol Malig Rep, 2, 69, 10.1007/s11899-007-0010-6

Cotter, 2000, Molecular abnormalities in chronic myeloid leukemia: deregulation of cell growth and apoptosis, Oncologist, 5, 405, 10.1634/theoncologist.5-5-405

Cortes, 2009, Molecular biology of bcr-abl1-positive chronic myeloid leukemia, Blood, 113, 1619, 10.1182/blood-2008-03-144790

Thomas, 1978, Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation, Exp Hematol, 6, 738

Tanzer, 1997, Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group, N Engl J Med, 337, 223, 10.1056/NEJM199707243370402

Druker, 2008, Translation of the Philadelphia chromosome into therapy for CML, Blood, 112, 4808, 10.1182/blood-2008-07-077958

Lydon, 1996, Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells, Nat Med, 2, 561, 10.1038/nm0596-561

Reiffers, 2006, Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia, N Engl J Med, 355, 2408, 10.1056/NEJMoa062867

Muller, 2008, ABL single nucleotide polymorphisms may masquerade as BCR-ABL mutations associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia, Haematologica, 93, 1389, 10.3324/haematol.12964

Boschelli, 2003, SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice, Cancer Res, 63, 375

Sawyers, 2004, Overriding imatinib resistance with a novel ABL kinase inhibitor, Science, 305, 399, 10.1126/science.1099480

Cavazza, 2005, Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl, Cancer Cell, 7, 129, 10.1016/j.ccr.2005.01.007

Sawyers, 2001, Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification, Science, 293, 876, 10.1126/science.1062538

Martinelli, 2007, Targeted therapy and the T315I mutation in Philadelphia-positive leukemias, Haematologica, 92, 437, 10.3324/haematol.11248

Cortes, 2008, Therapeutic options against BCR-ABL1 T315I-positive chronic myelogenous leukemia, Clin Cancer Res, 14, 4392, 10.1158/1078-0432.CCR-08-0117

Ning, 2009, AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance, Cancer Cell, 16, 401, 10.1016/j.ccr.2009.09.028

Holyoake, 2002, Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro, Blood, 99, 319, 10.1182/blood.V99.1.319

Bhatia, 2007, Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells, Blood, 109, 5411, 10.1182/blood-2006-06-032490

Druker, 2011, Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity, J Clin Invest, 121, 396, 10.1172/JCI35721

Rousselot, 2010, 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, 11, 1029, 10.1016/S1470-2045(10)70233-3

Yoshida, 1967, Clonal origin of chronic myelocytic leukemia in man, Proc Natl Acad Sci U S A, 58, 1468, 10.1073/pnas.58.4.1468

Nair, 1991, T-lymphoid blast crisis in chronic myeloid leukemia, Am J Hematol, 36, 86, 10.1002/ajh.2830360204

Gastl, 2000, Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells, Lancet, 355, 1688, 10.1016/S0140-6736(00)02241-8

Zhao, 2005, Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics, Blood, 105, 2733, 10.1182/blood-2004-07-2514

Loges, 2008, Blood outgrowth endothelial cells from chronic myeloid leukaemia patients are BCR/ABL1 negative, Br J Haematol, 142, 115, 10.1111/j.1365-2141.2008.07195.x

Baltimore, 1990, Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome, Science, 247, 824, 10.1126/science.2406902

Calabretta, 2002, BCR-ABL suppresses C/EBPalpha expression through inhibitory action of hnRNP E2, Nat Genet, 30, 48, 10.1038/ng791

Eaves, 2002, Elucidating critical mechanisms of deregulated stem cell turnover in the chronic phase of chronic myeloid leukemia, Leukemia, 16, 549, 10.1038/sj.leu.2402444

Eaves, 1983, Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia, N Engl J Med, 308, 1493, 10.1056/NEJM198306233082502

Turhan, 2010, Extensive analysis of the T315I substitution and detection of additional ABL mutations in progenitors and primitive stem cell compartment in a patient with tyrosine kinase inhibitor-resistant chronic myeloid leukemia, Leuk Lymphoma, 51, 2103, 10.3109/10428194.2010.520774

Eaves, 2010, Insights into the stem cells of chronic myeloid leukemia, Leukemia, 24, 1823, 10.1038/leu.2010.159

Eaves, 1992, Rapid decline of chronic myeloid leukemic cells in long-term culture due to a defect at the leukemic stem cell level, Proc Natl Acad Sci U S A, 89, 6192, 10.1073/pnas.89.13.6192

Eaves, 1986, Unregulated proliferation of primitive chronic myeloid leukemia progenitors in the presence of normal marrow adherent cells, Proc Natl Acad Sci U S A, 83, 5306, 10.1073/pnas.83.14.5306

Dick, 1994, A cell initiating human acute myeloid leukaemia after transplantation into SCID mice, Nature, 367, 645, 10.1038/367645a0

Dick, 1997, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell, Nat Med, 3, 730, 10.1038/nm0797-730

Turhan, 2001, Efficient ex vivo expansion of NOD/SCID-repopulating cells with lympho-myeloid potential in hematopoietic grafts of children with solid tumors, Hematol J, 2, 108, 10.1038/sj.thj.6200083

Eaves, 1999, Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia, Blood, 94, 2056, 10.1182/blood.V94.6.2056

Eaves, 1998, Differences between normal and CML stem cells: potential targets for clinical exploitation, Stem Cells, 16, 77

Jordan, 2011, Leukemia stem cells and microenvironment: biology and therapeutic targeting, J Clin Oncol, 29, 591, 10.1200/JCO.2010.31.0904

Morrison, 2005, SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells, Cell, 121, 1109, 10.1016/j.cell.2005.05.026

Scadden, 2003, Osteoblastic cells regulate the haematopoietic stem cell niche, Nature, 425, 841, 10.1038/nature02040

Rafii, 2005, The bone marrow vascular niche: home of HSC differentiation and mobilization, Physiology (Bethesda), 20, 349

Frenette, 2010, Mesenchymal and haematopoietic stem cells form a unique bone marrow niche, Nature, 466, 829, 10.1038/nature09262

Schuringa, 2006, Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche?, Hum Mol Genet, 15, R210

Gilliland, 2009, The leukemic stem cell niche: current concepts and therapeutic opportunities, Blood, 114, 1150, 10.1182/blood-2009-01-202606

Aurrand-Lions, 2011, JAM-B regulates maintenance of hematopoietic stem cells in the bone marrow, Blood

Viola, 2011, The critical role of agrin in the hematopoietic stem cell niche, Blood, 118, 2733, 10.1182/blood-2011-01-331272

Griffin, 1995, Increased tyrosine phosphorylation of focal adhesion proteins in myeloid cell lines expressing p210BCR/ABL, Oncogene, 11, 1149

Turhan, 2005, Osteopontin is upregulated by BCR-ABL, Biochem Biophys Res Commun, 333, 1378, 10.1016/j.bbrc.2005.05.203

Louache, 2005, p210BCR-ABL inhibits SDF-1 chemotactic response via alteration of CXCR4 signaling and down-regulation of CXCR4 expression, Cancer Res, 65, 2676, 10.1158/0008-5472.CAN-04-2152

Konopleva, 2008, CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells, Mol Cancer Ther, 7, 48, 10.1158/1535-7163.MCT-07-0042

Dias, 2011, Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia, Cancer Cell, 19, 740, 10.1016/j.ccr.2011.05.007

Hirao, 2010, TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia, Nature, 463, 676, 10.1038/nature08734

Apperley, 2009, Mechanisms of Resistance to Imatinib and Second-Generation Tyrosine Inhibitors in Chronic Myeloid Leukemia, Clin Cancer Res, 15, 7519, 10.1158/1078-0432.CCR-09-1068

Martinelli, 2009, Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib, Blood, 114, 5191, 10.1182/blood-2008-08-176016

Holyoake, 2006, Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction, Blood, 107, 4532, 10.1182/blood-2005-07-2947

Holyoake, 2007, Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells, Blood, 109, 4016, 10.1182/blood-2006-11-057521

Bhatia, 2008, Effective and selective inhibition of chronic myeloid leukemia primitive hematopoietic progenitors by the dual Src/Abl kinase inhibitor SKI-606, Blood, 111, 2329, 10.1182/blood-2007-05-092056

Eaves, 2007, Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies, Leukemia, 21, 926, 10.1038/sj.leu.2404609

Valent, 2008, Emerging stem cell concepts for imatinib-resistant chronic myeloid leukaemia: implications for the biology, management, and therapy of the disease, Br J Haematol, 142, 361, 10.1111/j.1365-2141.2008.07197.x

Sanchez-Garcia, 2009, Cancer induction by restriction of oncogene expression to the stem cell compartment, EMBO J, 28, 8, 10.1038/emboj.2008.253

Turhan, 2004, Evidence of ABL-kinase domain mutations in highly purified primitive stem cell populations of patients with chronic myelogenous leukemia, Biochem Biophys Res Commun, 323, 728, 10.1016/j.bbrc.2004.08.169

Bhatia, 2005, Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment, Blood, 105, 2093, 10.1182/blood-2004-03-1114

Turhan, 2009, Quantitative monitoring of the T315I mutation in patients with chronic myeloid leukemia (CML), Leuk Res, 33, 551, 10.1016/j.leukres.2008.08.018

Li, 2010, Novel therapeutic agents against cancer stem cells of chronic myeloid leukemia, Anticancer Agents Med Chem, 10, 111, 10.2174/187152010790909326

Peterson, 2011, Chronic myeloid leukemia stem cells and developing therapies, Leuk Lymphoma, 52, 60

Reya, 2007, Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo, Cancer Cell, 12, 528, 10.1016/j.ccr.2007.11.003

Li, 2009, beta-Catenin is essential for survival of leukemic stem cells insensitive to kinase inhibition in mice with BCR-ABL-induced chronic myeloid leukemia, Leukemia, 23, 109, 10.1038/leu.2008.262

Weissman, 2004, Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML, N Engl J Med, 351, 657, 10.1056/NEJMoa040258

Chiba, 2010, Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia, Blood, 115, 2872, 10.1182/blood-2009-05-222836

Warmuth, 2008, Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation, Cancer Cell, 14, 238, 10.1016/j.ccr.2008.08.003

Reya, 2009, Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia, Nature, 458, 776, 10.1038/nature07737

Scadden, 2008, Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo, Cell Stem Cell, 2, 274, 10.1016/j.stem.2008.01.003

Pandolfi, 2008, PML targeting eradicates quiescent leukaemia-initiating cells, Nature, 453, 1072, 10.1038/nature07016

Li, 2009, Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia, Nat Genet, 41, 783, 10.1038/ng.389

Jiang, 2008, AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells, J Exp Med, 205, 2657, 10.1084/jem.20072316

Li, 2007, Inhibition of heat shock protein 90 prolongs survival of mice with BCR-ABL-T315I-induced leukemia and suppresses leukemic stem cells, Blood, 110, 678, 10.1182/blood-2006-10-054098

Sexl, 2011, High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia, Blood, 117, 3409, 10.1182/blood-2009-10-248211

Frank, 2011, The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors, Blood, 117, 3421, 10.1182/blood-2009-11-255232

Turhan, 2011, STAT5 as a CML target: STATinib therapies?, Blood, 117, 3252, 10.1182/blood-2011-01-332569

Radich, 2009, Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet, J Clin Oncol, 27, 6041, 10.1200/JCO.2009.25.0779

Martinelli, 2011, BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet, Blood, 118, 1208, 10.1182/blood-2010-12-326405

Gonzalez, 2003, Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program, Leukemia, 17, 2318, 10.1038/sj.leu.2403135

Gabert, 2003, Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) - a Europe against cancer program, Leukemia, 17, 2474, 10.1038/sj.leu.2403135

Hughes, 2008, Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials, Blood, 112, 3330, 10.1182/blood-2008-04-150680

Jones, 2010, Establishment of the first World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL mRNA, Blood, 116, e111, 10.1182/blood-2010-06-291641

Goldman, 2007, How I treat chronic myeloid leukemia in the imatinib era, Blood, 110, 2828, 10.1182/blood-2007-04-038943

Nowak, 2005, Dynamics of chronic myeloid leukaemia, Nature, 435, 1267, 10.1038/nature03669

Loeffler, 2006, Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications, Nat Med, 12, 1181, 10.1038/nm1487

Michor, 2011, Dynamics of chronic myeloid leukemia response to long-term targeted therapy reveal treatment effects on leukemic stem cells, Blood, 118, 1622, 10.1182/blood-2011-02-339267

Michor, 2007, Chronic myeloid leukemia blast crisis arises from progenitors, Stem Cells, 25, 1114, 10.1634/stemcells.2006-0638

Michor, 2009, Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib, PLoS Comput Biol, 5, e1000503, 10.1371/journal.pcbi.1000503

Wodarz, 2007, Effect of cellular quiescence on the success of targeted CML therapy, PLoS One, 2, e990, 10.1371/journal.pone.0000990

Gordon, 2006, Why do chronic myelogenous leukemia stem cells survive allogeneic stem cell transplantation or imatinib: does it really matter?, Leuk Lymphoma, 47, 1, 10.1080/10428190500407996

Turhan, 2011, Leukemic stem cell persistency in chronic myeloid leukemia patients with sustained undetectable molecular residual disease, Blood

Reiffers, 2002, Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa, J Clin Oncol, 20, 214, 10.1200/JCO.2002.20.1.214

Graeven, 2006, Continuous complete hematological and cytogenetic remission with molecular minimal residual disease 9 years after discontinuation of interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia, Acta Haematol, 115, 109, 10.1159/000089476

Jones, 2005, Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors, Br J Haematol, 130, 373, 10.1111/j.1365-2141.2005.05606.x

Trumpp, 2009, IFNalpha activates dormant haematopoietic stem cells in vivo, Nature, 458, 904, 10.1038/nature07815

Wilson, 2010, Awakening dormant haematopoietic stem cells, Nat Rev Immunol, 10, 201, 10.1038/nri2726

Kantarjian, 2004, Discontinuation of imatinib therapy after achieving a molecular response, Blood, 104, 2204, 10.1182/blood-2004-04-1335

Maziarz, 2004, Divergent clinical outcome in two CML patients who discontinued imatinib therapy after achieving a molecular remission, Leuk Res, 28, S71

Lazzarino, 2005, Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation, Haematologica, 90, 979

Mahon, 2007, Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years, Blood, 109, 58, 10.1182/blood-2006-03-011239

Cortes, 2008, Sustained complete molecular response after imatinib discontinuation in a patient with chronic myeloid leukemia not previously exposed to interferon alpha, Leuk Lymphoma, 49, 1399, 10.1080/10428190802043903

Sica, 2009, Is it possible to discontinue imatinib mesylate therapy in Chronic Myeloid Leukemia patients with undetectable BCR/ABL? A case report and a review of the literature, Leuk Res, 33, 1079, 10.1016/j.leukres.2008.11.027

Hughes, 2010, Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR, Leukemia, 24, 1719, 10.1038/leu.2010.185

Melo, 2010, In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib, Blood, 116, 1329, 10.1182/blood-2009-11-255109

Naoe, 2008, Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy, Int J Hematol, 88, 471, 10.1007/s12185-008-0221-1

Brizard, 2000, Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-alpha therapy or allogeneic bone marrow transplantation, Blood, 95, 404, 10.1182/blood.V95.2.404

Kurzrock, 1994, Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies, J Clin Invest, 94, 1383, 10.1172/JCI117473

Forman, 2003, Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment, Blood, 101, 4701, 10.1182/blood-2002-09-2780

Lauria, 2008, CD34+/Ph+ cells are still detectable in chronic myeloid leukemia patients with sustained and prolonged complete cytogenetic remission during treatment with imatinib mesylate, Leukemia, 22, 426, 10.1038/sj.leu.2404893

Porkka, 2010, Low or undetectable numbers of Philadelphia chromosome-positive leukemic stem cells (Ph(+)CD34(+)CD38(neg)) in chronic myeloid leukemia patients in complete cytogenetic remission after tyrosine kinase inhibitor therapy, Leukemia, 24, 219, 10.1038/leu.2009.190

Fichelson, 2003, Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein, Nat Med, 9, 1423, 10.1038/nm953

Laraya, 1994, Variable transcription of BCR-ABL by Ph+ cells arising from hematopoietic progenitors in chronic myeloid leukemia, Blood, 83, 1744, 10.1182/blood.V83.7.1744.1744

Melo, 2011, Do we have to kill the last CML cell?, Leukemia, 25, 193, 10.1038/leu.2010.197

Holyoake, 2005, Punish the parent not the progeny, Blood, 105, 1862, 10.1182/blood-2004-08-3373