{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:34:34Z","timestamp":1791232474966,"version":"4.1.0"},"reference-count":95,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","theclinics.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Hematology\/Oncology Clinics of North America"],"published-print":{"date-parts":[[2011,10]]},"DOI":"10.1016\/j.hoc.2011.09.001","type":"journal-article","created":{"date-parts":[[2011,10,22]],"date-time":"2011-10-22T19:24:55Z","timestamp":1319311495000},"page":"951-966","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hurdles Toward a Cure for CML: The CML Stem Cell"],"prefix":"10.1016","volume":"25","author":[{"given":"Paolo","family":"Gallipoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela A.","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa L.","family":"Holyoake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"17","key":"10.1016\/j.hoc.2011.09.001_bib1","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1056\/NEJM199904293401706","article-title":"Chronic myeloid leukemia","volume":"340","author":"Sawyers","year":"1999","journal-title":"N\u00a0Engl J Med"},{"issue":"23","key":"10.1016\/j.hoc.2011.09.001_bib2","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1056\/NEJMoa062867","article-title":"Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia","volume":"355","author":"Druker","year":"2006","journal-title":"N\u00a0Engl J Med"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib3","doi-asserted-by":"crossref","first-page":"5401","DOI":"10.1182\/blood-2008-12-196543","article-title":"Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study","volume":"113","author":"Noens","year":"2009","journal-title":"Blood"},{"issue":"14","key":"10.1016\/j.hoc.2011.09.001_bib4","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1200\/JCO.2009.26.3087","article-title":"Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib","volume":"28","author":"Marin","year":"2010","journal-title":"J\u00a0Clin Oncol"},{"issue":"3","key":"10.1016\/j.hoc.2011.09.001_bib5","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrc1567","article-title":"Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia","volume":"5","author":"Ren","year":"2005","journal-title":"Nat Rev Cancer"},{"issue":"7046","key":"10.1016\/j.hoc.2011.09.001_bib6","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/nature03669","article-title":"Dynamics of chronic myeloid leukaemia","volume":"435","author":"Michor","year":"2005","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00109-007-0241-y","article-title":"Pathogenesis, treatment effects, and resistance dynamics in chronic myeloid leukemia\u2014insights from mathematical model analyses","volume":"86","author":"Roeder","year":"2008","journal-title":"J\u00a0Mol Med"},{"issue":"13","key":"10.1016\/j.hoc.2011.09.001_bib8","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1182\/blood-2008-08-077941","article-title":"Stem cell concepts renew cancer research","volume":"112","author":"Dick","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.hoc.2011.09.001_bib9","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/197452a0","article-title":"Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells","volume":"197","author":"Becker","year":"1963","journal-title":"Nature"},{"issue":"4260","key":"10.1016\/j.hoc.2011.09.001_bib10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1126\/science.959840","article-title":"The clonal evolution of tumor cell populations","volume":"194","author":"Nowell","year":"1976","journal-title":"Science"},{"issue":"6464","key":"10.1016\/j.hoc.2011.09.001_bib11","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/367645a0","article-title":"A\u00a0cell initiating human acute myeloid leukaemia after transplantation into SCID mice","volume":"367","author":"Lapidot","year":"1994","journal-title":"Nature"},{"issue":"7","key":"10.1016\/j.hoc.2011.09.001_bib12","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nm0797-730","article-title":"Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell","volume":"3","author":"Bonnet","year":"1997","journal-title":"Nat Med"},{"issue":"19","key":"10.1016\/j.hoc.2011.09.001_bib13","doi-asserted-by":"crossref","first-page":"9339","DOI":"10.1158\/0008-5472.CAN-06-3126","article-title":"Cancer stem cells\u2014perspectives on current status and future directions: AACR Workshop on cancer stem cells","volume":"66","author":"Clarke","year":"2006","journal-title":"Cancer Res"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/leu.2008.246","article-title":"Targeting the leukemic stem cell: the Holy Grail of leukemia therapy","volume":"23","author":"Misaghian","year":"2009","journal-title":"Leukemia"},{"issue":"6","key":"10.1016\/j.hoc.2011.09.001_bib15","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1182\/blood-2009-01-202606","article-title":"The leukemic stem cell niche: current concepts and therapeutic opportunities","volume":"114","author":"Lane","year":"2009","journal-title":"Blood"},{"issue":"10","key":"10.1016\/j.hoc.2011.09.001_bib16","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/bies.200900058","article-title":"Identification and targeting of cancer stem cells","volume":"31","author":"Schatton","year":"2009","journal-title":"Bioessays"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1172\/JCI41004","article-title":"The therapeutic promise of the cancer stem cell concept","volume":"120","author":"Frank","year":"2010","journal-title":"J\u00a0Clin Invest"},{"issue":"5861","key":"10.1016\/j.hoc.2011.09.001_bib18","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1126\/science.1150648","article-title":"Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia","volume":"319","author":"Hong","year":"2008","journal-title":"Science"},{"issue":"7222","key":"10.1016\/j.hoc.2011.09.001_bib19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nature07567","article-title":"Efficient tumour formation by single human melanoma cells","volume":"456","author":"Quintana","year":"2008","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib20","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.cell.2009.08.017","article-title":"Heterogeneity in cancer: cancer stem cells versus clonal evolution","volume":"138","author":"Shackleton","year":"2009","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib21","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nbt0109-44","article-title":"Looking ahead in cancer stem cell research","volume":"27","author":"Dick","year":"2009","journal-title":"Nat Biotechnol"},{"issue":"19","key":"10.1016\/j.hoc.2011.09.001_bib22","doi-asserted-by":"crossref","first-page":"7882","DOI":"10.1158\/0008-5472.CAN-08-0723","article-title":"Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines","volume":"68","author":"Jaksch","year":"2008","journal-title":"Cancer Res"},{"issue":"5836","key":"10.1016\/j.hoc.2011.09.001_bib23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1126\/science.1142596","article-title":"Tumor growth need not be driven by rare cancer stem cells","volume":"317","author":"Kelly","year":"2007","journal-title":"Science"},{"issue":"5857","key":"10.1016\/j.hoc.2011.09.001_bib24","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1126\/science.1149590","article-title":"Comment on \u201cTumor growth need not be driven by rare cancer stem cells\u201d","volume":"318","author":"Kennedy","year":"2007","journal-title":"Science"},{"issue":"7176","key":"10.1016\/j.hoc.2011.09.001_bib25","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature06489","article-title":"Identification of cells initiating human melanomas","volume":"451","author":"Schatton","year":"2008","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.hoc.2011.09.001_bib26","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1200\/JCO.2009.25.4896","article-title":"Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase","volume":"28","author":"Cortes","year":"2010","journal-title":"J\u00a0Clin Oncol"},{"issue":"3","key":"10.1016\/j.hoc.2011.09.001_bib27","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1200\/JCO.2009.25.4920","article-title":"Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia","volume":"28","author":"Cortes","year":"2010","journal-title":"J\u00a0Clin Oncol"},{"issue":"6","key":"10.1016\/j.hoc.2011.09.001_bib28","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1182\/blood.V94.6.2056","article-title":"Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia","volume":"94","author":"Holyoake","year":"1999","journal-title":"Blood"},{"issue":"9","key":"10.1016\/j.hoc.2011.09.001_bib29","doi-asserted-by":"crossref","first-page":"4016","DOI":"10.1182\/blood-2006-11-057521","article-title":"Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells","volume":"109","author":"Jorgensen","year":"2007","journal-title":"Blood"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib30","doi-asserted-by":"crossref","first-page":"4532","DOI":"10.1182\/blood-2005-07-2947","article-title":"Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction","volume":"107","author":"Copland","year":"2006","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib31","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1182\/blood.V99.1.319","article-title":"Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in\u00a0vitro","volume":"99","author":"Graham","year":"2002","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.hoc.2011.09.001_bib32","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/sj.leu.2405086","article-title":"Enhanced BCR-ABL kinase inhibition does not result in increased inhibition of downstream signaling pathways or increased growth suppression in CML progenitors","volume":"22","author":"Konig","year":"2008","journal-title":"Leukemia"},{"issue":"4","key":"10.1016\/j.hoc.2011.09.001_bib33","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1182\/blood-2007-05-092056","article-title":"Effective and selective inhibition of chronic myeloid leukemia primitive hematopoietic progenitors by the dual Src\/Abl kinase inhibitor SKI-606","volume":"111","author":"Konig","year":"2008","journal-title":"Blood"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1182\/blood.V112.11.194.194","article-title":"Persistence of leukemia stem cells in chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib treatment for 5 years","volume":"112","author":"Chu","year":"2008","journal-title":"Blood"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib35","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V114.22.859.859","article-title":"Discontinuation of imatinib therapy after achieving a molecular response in chronic myeloid leukemia patients","volume":"114","author":"Mahon","year":"2009","journal-title":"Blood"},{"issue":"9","key":"10.1016\/j.hoc.2011.09.001_bib36","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1158\/0008-5472.CAN-07-3293","article-title":"Oncogene addiction","volume":"68","author":"Weinstein","year":"2008","journal-title":"Cancer Res"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib37","doi-asserted-by":"crossref","first-page":"101a","DOI":"10.1182\/blood.V110.11.320.320","article-title":"Responses and disease progression in CML-CP patients treated with nilotinib after imatinib failure appear to be affected by the BCR-ABL mutation status and types","volume":"110","author":"Hughes","year":"2007","journal-title":"Blood"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib38","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/sj.leu.2404609","article-title":"Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies","volume":"21","author":"Jiang","year":"2007","journal-title":"Leukemia"},{"issue":"6","key":"10.1016\/j.hoc.2011.09.001_bib39","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1182\/blood.V101.6.2368","article-title":"MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models","volume":"101","author":"Mahon","year":"2003","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.hoc.2011.09.001_bib40","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/leu.2010.16","article-title":"Chronic myeloid leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 activity","volume":"24","author":"Engler","year":"2010","journal-title":"Leukemia"},{"issue":"4","key":"10.1016\/j.hoc.2011.09.001_bib41","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1182\/blood-2006-02-003145","article-title":"Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate","volume":"108","author":"Jordanides","year":"2006","journal-title":"Blood"},{"issue":"7","key":"10.1016\/j.hoc.2011.09.001_bib42","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1158\/0008-5472.CAN-03-3344","article-title":"Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in\u00a0vitro","volume":"64","author":"Houghton","year":"2004","journal-title":"Cancer Res"},{"issue":"9","key":"10.1016\/j.hoc.2011.09.001_bib43","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1182\/blood-2004-04-1398","article-title":"Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)\/ABCG2 drug pump","volume":"104","author":"Burger","year":"2004","journal-title":"Blood"},{"issue":"6","key":"10.1016\/j.hoc.2011.09.001_bib44","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.exphem.2009.02.006","article-title":"Inhibition of MDR1 does not\u00a0sensitize primitive chronic myeloid leukemia CD34+ cells to imatinib","volume":"37","author":"Hatziieremia","year":"2009","journal-title":"Exp Hematol"},{"issue":"12","key":"10.1016\/j.hoc.2011.09.001_bib45","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1182\/blood-2007-06-093617","article-title":"Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity","volume":"110","author":"White","year":"2007","journal-title":"Blood"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib46","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1038\/leu.2009.166","article-title":"Nilotinib concentration in cell lines and primary CD34(+) chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters","volume":"23","author":"Davies","year":"2009","journal-title":"Leukemia"},{"issue":"10","key":"10.1016\/j.hoc.2011.09.001_bib47","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1182\/blood.V92.10.3829.422k14_3829_3840","article-title":"Bcr-Abl efficiently induces a myeloproliferative disease and production of excess interleukin-3 and granulocyte-macrophage colony-stimulating factor in mice: a novel model for chronic myelogenous leukemia","volume":"92","author":"Zhang","year":"1998","journal-title":"Blood"},{"issue":"10","key":"10.1016\/j.hoc.2011.09.001_bib48","doi-asserted-by":"crossref","first-page":"6918","DOI":"10.1128\/MCB.19.10.6918","article-title":"Bcr-Abl with an SH3 deletion retains the ability To induce a myeloproliferative disease in mice, yet c-Abl activated by an SH3 deletion induces only lymphoid malignancy","volume":"19","author":"Gross","year":"1999","journal-title":"Mol Cell Biol"},{"issue":"10","key":"10.1016\/j.hoc.2011.09.001_bib49","doi-asserted-by":"crossref","first-page":"e7439","DOI":"10.1371\/journal.pone.0007439","article-title":"A\u00a0BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice","volume":"4","author":"Johnson","year":"2009","journal-title":"PLoS One"},{"issue":"6","key":"10.1016\/j.hoc.2011.09.001_bib50","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.ccr.2004.10.015","article-title":"MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors","volume":"6","author":"Huntly","year":"2004","journal-title":"Cancer Cell"},{"issue":"16","key":"10.1016\/j.hoc.2011.09.001_bib51","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1182\/blood-2009-04-215376","article-title":"BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells","volume":"115","author":"Schemionek","year":"2010","journal-title":"Blood"},{"issue":"14 Pt 2","key":"10.1016\/j.hoc.2011.09.001_bib52","doi-asserted-by":"crossref","first-page":"4392s","DOI":"10.1158\/1078-0432.CCR-06-0096","article-title":"\u201cOncogenic shock\u201d: explaining oncogene addiction through differential signal attenuation","volume":"12","author":"Sharma","year":"2006","journal-title":"Clin Cancer Res"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib53","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ccr.2006.09.014","article-title":"A\u00a0common signaling cascade may underlie \u201caddiction\u201d to the Src, BCR-ABL, and EGF receptor oncogenes","volume":"10","author":"Sharma","year":"2006","journal-title":"Cancer Cell"},{"issue":"45","key":"10.1016\/j.hoc.2011.09.001_bib54","doi-asserted-by":"crossref","first-page":"16870","DOI":"10.1073\/pnas.0606509103","article-title":"Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice","volume":"103","author":"Hu","year":"2006","journal-title":"Proc Natl Acad Sci U\u00a0S\u00a0A"},{"issue":"2","key":"10.1016\/j.hoc.2011.09.001_bib55","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1158\/0008-5472.CAN-03-1484","article-title":"Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia","volume":"64","author":"Donato","year":"2004","journal-title":"Cancer Res"},{"issue":"7239","key":"10.1016\/j.hoc.2011.09.001_bib56","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature07737","article-title":"Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia","volume":"458","author":"Zhao","year":"2009","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.hoc.2011.09.001_bib57","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ccr.2008.08.003","article-title":"Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation","volume":"14","author":"Dierks","year":"2008","journal-title":"Cancer Cell"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib58","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V114.22.1428.1428","article-title":"Combination of the hedgehog pathway inhibitor LDE225 and nilotinib eliminates chronic myeloid leukemia stem and progenitor cells","volume":"114","author":"Irvine","year":"2009","journal-title":"Blood"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib59","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/cr.2008.47","article-title":"Wnt signaling and stem cell control","volume":"18","author":"Nusse","year":"2008","journal-title":"Cell Res"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib60","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/leu.2008.262","article-title":"beta-Catenin is essential for survival of leukemic stem cells insensitive to kinase inhibition in mice with BCR-ABL-induced chronic myeloid leukemia","volume":"23","author":"Hu","year":"2009","journal-title":"Leukemia"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib61","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V114.22.2168.2168","article-title":"Wnt-pathway directed compound targets blast crisis and chronic phase CML leukemia stem progenitors","volume":"114","author":"Peterson","year":"2009","journal-title":"Blood"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib62","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.ccr.2005.10.015","article-title":"The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR\/ABL-regulated SET protein","volume":"8","author":"Neviani","year":"2005","journal-title":"Cancer Cell"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib63","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V112.11.189.189","article-title":"Activation of PP2A by FTY720 inhibits survival and self-renewal of the Ph(+) chronic myelogenous leukemia (CML) CD34+\/CD38\u2013 stem cell through the simultaneous suppression of BCR\/ABL and BCR\/ABL\u2013 independent signals","volume":"112","author":"Neviani","year":"2008","journal-title":"Blood"},{"issue":"7281","key":"10.1016\/j.hoc.2011.09.001_bib64","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nature08734","article-title":"TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia","volume":"463","author":"Naka","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.hoc.2011.09.001_bib65","unstructured":"Pellicano F, Huntly BJ, Holyoake TL. Investigation of the role of FOXO in TKI-induced G1 arrest as potential targets in CML stem\/progenitor cell eradication. Abstract presented at ESH-EHA Scientific Workshop Leukemic and Cancer Stem Cells. Mandelieu (France), April 3\u20135, 2009."},{"issue":"2","key":"10.1016\/j.hoc.2011.09.001_bib66","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1158\/1078-0432.CCR-05-0429","article-title":"Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in\u00a0vitro promotes their elimination by imatinib mesylate","volume":"12","author":"Jorgensen","year":"2006","journal-title":"Clin Cancer Res"},{"issue":"3","key":"10.1016\/j.hoc.2011.09.001_bib67","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1158\/0008-5472.CAN-06-2014","article-title":"Growth factor stimulation reduces residual quiescent chronic myelogenous leukemia progenitors remaining after imatinib treatment","volume":"67","author":"Holtz","year":"2007","journal-title":"Cancer Res"},{"issue":"6","key":"10.1016\/j.hoc.2011.09.001_bib68","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/leu.2009.43","article-title":"A\u00a0pilot study of continuous imatinib vs pulsed imatinib with or without G-CSF in CML patients who have achieved a complete cytogenetic response","volume":"23","author":"Drummond","year":"2009","journal-title":"Leukemia"},{"issue":"2","key":"10.1016\/j.hoc.2011.09.001_bib69","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(02)00626-8","article-title":"The role of PML in tumor suppression","volume":"108","author":"Salomoni","year":"2002","journal-title":"Cell"},{"issue":"7198","key":"10.1016\/j.hoc.2011.09.001_bib70","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/nature07016","article-title":"PML targeting eradicates quiescent leukaemia-initiating cells","volume":"453","author":"Ito","year":"2008","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.hoc.2011.09.001_bib71","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/cncr.21590","article-title":"Pilot study of lonafarnib, a farnesyl transferase inhibitor, in patients with chronic myeloid leukemia in the chronic or accelerated phase that is resistant or refractory to imatinib therapy","volume":"106","author":"Borthakur","year":"2006","journal-title":"Cancer"},{"issue":"7","key":"10.1016\/j.hoc.2011.09.001_bib72","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/sj.leu.2403785","article-title":"Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in\u00a0vitro","volume":"19","author":"Jorgensen","year":"2005","journal-title":"Leukemia"},{"issue":"12","key":"10.1016\/j.hoc.2011.09.001_bib73","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.1167\/iovs.08-2348","article-title":"The clinical time-course of experimental autoimmune uveoretinitis using topical endoscopic fundal imaging with histologic and cellular infiltrate correlation","volume":"49","author":"Copland","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"19","key":"10.1016\/j.hoc.2011.09.001_bib74","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1182\/blood-2009-05-219550","article-title":"BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem\/progenitor cells, including CD34+38\u2013 cells, through activation of protein kinase Cbeta","volume":"114","author":"Pellicano","year":"2009","journal-title":"Blood"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib75","doi-asserted-by":"crossref","first-page":"12804","DOI":"10.1073\/pnas.96.22.12804","article-title":"Autocrine production and action of IL-3 and granulocyte colony-stimulating factor in chronic myeloid leukemia","volume":"96","author":"Jiang","year":"1999","journal-title":"Proc Natl Acad Sci U\u00a0S\u00a0A"},{"issue":"4","key":"10.1016\/j.hoc.2011.09.001_bib76","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/leu.2009.299","article-title":"Blocking cytokine signaling along with intense Bcr-Abl kinase inhibition induces apoptosis in primary CML progenitors","volume":"24","author":"Hiwase","year":"2010","journal-title":"Leukemia"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib77","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1182\/blood-2006-08-040022","article-title":"Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR\/ABL+ progenitors via JAK-2\/STAT-5 pathway activation","volume":"109","author":"Wang","year":"2007","journal-title":"Blood"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib78","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V114.22.39.39","article-title":"Jak2 phosphorylates Tyr 177 of Bcr-Abl activating the Ras and PI-3 kinase pathways and maintains functional levels of Bcr-Abl in chronic myelogenous leukemia","volume":"114","author":"Samanta","year":"2009","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib79","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.phrs.2010.02.010","article-title":"Histone deacetylases and epigenetic therapies of hematological malignancies","volume":"62","author":"Mercurio","year":"2010","journal-title":"Pharm Res"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib80","article-title":"Effective targeting of quiescent CML stem cells by histone deacetylase inhibitors in combination with imatinib mesylate","volume":"114","author":"Zhang","year":"2009","journal-title":"Blood"},{"issue":"22","key":"10.1016\/j.hoc.2011.09.001_bib81","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V114.22.2194.2194","article-title":"A\u00a0phase I study of the HDAC inhibitor LBH589 in combination with imatinib for patients with CML in cytogenetic remission with residual disease detectable by Q-PCR","volume":"114","author":"Bhatia","year":"2009","journal-title":"Blood"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib82","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1182\/blood-2008-06-164582","article-title":"Bortezomib induces apoptosis in primitive chronic myeloid leukemia cells including LTC-IC and NOD\/SCID repopulating cells","volume":"115","author":"Heaney","year":"2010","journal-title":"Blood"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib83","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrm2245","article-title":"Autophagy: from phenomenology to molecular understanding in less than a decade","volume":"8","author":"Klionsky","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"2","key":"10.1016\/j.hoc.2011.09.001_bib84","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cell.2004.11.046","article-title":"Growth factor regulation of autophagy and cell survival in the absence of apoptosis","volume":"120","author":"Lum","year":"2005","journal-title":"Cell"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib85","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1172\/JCI35660","article-title":"Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells","volume":"119","author":"Bellodi","year":"2009","journal-title":"J\u00a0Clin Invest"},{"issue":"5","key":"10.1016\/j.hoc.2011.09.001_bib86","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1182\/blood.V86.5.2041.bloodjournal8652041","article-title":"Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients","volume":"86","author":"Kolb","year":"1995","journal-title":"Blood"},{"issue":"12","key":"10.1016\/j.hoc.2011.09.001_bib87","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1182\/blood.V76.12.2462.2462","article-title":"Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients","volume":"76","author":"Kolb","year":"1990","journal-title":"Blood"},{"issue":"11","key":"10.1016\/j.hoc.2011.09.001_bib88","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1038\/sj.leu.2404858","article-title":"Clinical evaluation of BCR-ABL peptide immunisation in chronic myeloid leukaemia: results of the EPIC study","volume":"21","author":"Rojas","year":"2007","journal-title":"Leukemia"},{"issue":"17","key":"10.1016\/j.hoc.2011.09.001_bib89","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1002\/cncr.24468","article-title":"Synthetic tumor-specific breakpoint peptide vaccine in patients with chronic myeloid leukemia and minimal residual disease: a phase 2 trial","volume":"115","author":"Jain","year":"2009","journal-title":"Cancer"},{"issue":"1","key":"10.1016\/j.hoc.2011.09.001_bib90","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1158\/1078-0432.CCR-09-2046","article-title":"K562\/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate","volume":"16","author":"Smith","year":"2010","journal-title":"Clin Cancer Res"},{"issue":"8","key":"10.1016\/j.hoc.2011.09.001_bib91","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1038\/leu.2008.7","article-title":"A\u00a0pilot vaccination trial of synthetic analog peptides derived from the BCR-ABL breakpoints in CML patients with minimal disease","volume":"22","author":"Maslak","year":"2008","journal-title":"Leukemia"},{"issue":"12","key":"10.1016\/j.hoc.2011.09.001_bib92","doi-asserted-by":"crossref","first-page":"4460","DOI":"10.1158\/1078-0432.CCR-05-0250","article-title":"Combination of imatinib mesylate with autologous leukocyte-derived heat shock protein and chronic myelogenous leukemia","volume":"11","author":"Li","year":"2005","journal-title":"Clin Cancer Res"},{"issue":"4","key":"10.1016\/j.hoc.2011.09.001_bib93","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/cncr.11223","article-title":"Complete cytogenetic and molecular responses to interferon-alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis","volume":"97","author":"Kantarjian","year":"2003","journal-title":"Cancer"},{"issue":"9","key":"10.1016\/j.hoc.2011.09.001_bib94","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/79526","article-title":"Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia","volume":"6","author":"Molldrem","year":"2000","journal-title":"Nat Med"},{"issue":"8","key":"10.1016\/j.hoc.2011.09.001_bib95","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1200\/JCO.2009.25.5075","article-title":"Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia","volume":"28","author":"Burchert","year":"2010","journal-title":"J\u00a0Clin Oncol"}],"container-title":["Hematology\/Oncology Clinics of North America"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889858811000980?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889858811000980?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T11:55:03Z","timestamp":1760183703000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0889858811000980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10]]},"references-count":95,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,10]]}},"alternative-id":["S0889858811000980"],"URL":"https:\/\/doi.org\/10.1016\/j.hoc.2011.09.001","relation":{},"ISSN":["0889-8588"],"issn-type":[{"value":"0889-8588","type":"print"}],"subject":[],"published":{"date-parts":[[2011,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hurdles Toward a Cure for CML: The CML Stem Cell","name":"articletitle","label":"Article Title"},{"value":"Hematology\/Oncology Clinics of North America","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.hoc.2011.09.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2011 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}