{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T22:09:46Z","timestamp":1787436586068,"version":"build-2736575974"},"reference-count":101,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T00:00:00Z","timestamp":1503360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>All blood lineage cells are generated from hematopoietic stem cells (HSCs), which reside in bone marrow after birth. HSCs self-renew, proliferate, and differentiate into mature progeny under the control of local microenvironments including hematopoietic niche, which can deliver regulatory signals in the form of bound or secreted molecules and from physical cues such as oxygen tension and shear stress. Among these mediators, accumulating evidence indicates the potential involvement of several chemokines, particularly CXCL12, in the interaction between HSCs and bone marrow microenvironments. Fusion between breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog (ABL)-1 gene gives rise to BCR-ABL protein with a constitutive tyrosine kinase activity and transforms HSCs and\/or hematopoietic progenitor cells (HPCs) into disease-propagating leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). LSCs can self-renew, proliferate, and differentiate under the influence of the signals delivered by bone marrow microenvironments including niche, as HSCs can. Thus, the interaction with bone marrow microenvironments is indispensable for the initiation, maintenance, and progression of CML. Moreover, the crosstalk between LSCs and bone marrow microenvironments can contribute to some instances of therapeutic resistance. Furthermore, evidence is accumulating to indicate the important roles of bone marrow microenvironment-derived chemokines. Hence, we will herein discuss the roles of chemokines in CML with a focus on bone marrow microenvironments.<\/jats:p>","DOI":"10.3390\/ijms18081824","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T11:08:25Z","timestamp":1503400105000},"page":"1824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"18","author":[{"given":"Naofumi","family":"Mukaida","sequence":"first","affiliation":[{"name":"Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Ishikawa, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamato","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Ishikawa, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2161-2087","authenticated-orcid":false,"given":"Tomohisa","family":"Baba","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Ishikawa, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature12984","article-title":"The bone marrow niche for haematopoietic stem cells","volume":"505","author":"Morrison","year":"2014","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/nyas.12986","article-title":"Regulation of hematopoietic stem cell integrity through p53 and its related factors","volume":"1370","author":"Yamashita","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1038\/emboj.2013.201","article-title":"Haematopoietic stem cell niches: New insights inspire new questions","volume":"32","author":"Ugarte","year":"2013","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1182\/blood-2016-11-696070","article-title":"The microenvironment in human myeloid malignancies: Emerging concepts and therapeutic implications","volume":"129","author":"Medyouf","year":"2017","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1182\/blood-2016-09-670224","article-title":"Myeloid malignancies and the microenvironment","volume":"129","author":"Korn","year":"2017","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.1073\/pnas.96.6.3120","article-title":"In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells","volume":"96","author":"Cheshier","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s00109-014-1123-8","article-title":"CXC chemokine ligand 12 (CXCL12) and its receptor CXCR4","volume":"92","author":"Nagasawa","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1158\/1078-0432.CCR-07-5134","article-title":"Regulation of hematopoietic stem cells by the steel factor\/KIT signaling pathway","volume":"14","author":"Kent","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1084\/jem.192.9.1365","article-title":"The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells","volume":"192","author":"Karanu","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/84282","article-title":"Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation","volume":"2","author":"Bhardwaj","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nature01593","article-title":"A role for WNT signalling in self-renewal of haematopoietic stem cells","volume":"423","author":"Reya","year":"2003","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1182\/blood-2014-12-618090","article-title":"TGF-\u03b2 signaling in the control of hematopoietic stem cells","volume":"125","author":"Blank","year":"2015","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1182\/blood-2012-04-424507","article-title":"Two anatomically distinct niches regulate stem cell activity","volume":"120","author":"Ema","year":"2012","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.cell.2005.05.026","article-title":"Slam family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells","volume":"121","author":"Kiel","year":"2005","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nm.3647","article-title":"Hematopoietic stem cell niche maintenance during homeostasis and regeneration","volume":"20","author":"Mendelson","year":"2014","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1126\/science.1064081","article-title":"Physiological migration of hematopoietic stem and progenitor cells","volume":"294","author":"Wright","year":"2001","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/nature03703","article-title":"In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment","volume":"435","author":"Sipkins","year":"2005","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng1149","article-title":"Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease","volume":"34","author":"Hernandez","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.cell.2015.01.014","article-title":"Chromothriptic cure of WHIM syndrome","volume":"160","author":"McDermott","year":"2015","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1084\/jem.20072513","article-title":"CXCR4 is required for the quiescence of primitive hematopoietic cells","volume":"205","author":"Nie","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cell.2007.08.025","article-title":"Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment","volume":"131","author":"Sacchetti","year":"2007","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.immuni.2006.10.016","article-title":"Maintenance of the hematopoietic stem cell pool by CXCL12\u2013CXCR4 chemokine signaling in bone marrow stromal cell niches","volume":"25","author":"Sugiyama","year":"2006","journal-title":"Immunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature10783","article-title":"Endothelial and perivascular cells maintain haematopoietic stem cells","volume":"481","author":"Ding","year":"2012","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/ncb3475","article-title":"Differential cytokine contributions of perivascular haematopoietic stem cell niches","volume":"19","author":"Asada","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/382635a0","article-title":"Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF\/SDF-1","volume":"382","author":"Nagasawa","year":"1996","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/31261","article-title":"The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract","volume":"393","author":"Tachibana","year":"1998","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/31269","article-title":"Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development","volume":"393","author":"Zou","year":"1998","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9448","DOI":"10.1073\/pnas.95.16.9448","article-title":"Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice","volume":"95","author":"Ma","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature11885","article-title":"Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches","volume":"495","author":"Ding","year":"2013","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.immuni.2010.08.017","article-title":"The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche","volume":"33","author":"Omatsu","year":"2010","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nature11926","article-title":"CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance","volume":"495","author":"Greenbaum","year":"2013","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nature06685","article-title":"Haematopoietic stem cell release is regulated by circadian oscillations","volume":"452","author":"Lucas","year":"2008","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.immuni.2012.05.008","article-title":"The chemokine superfamily revisited","volume":"36","author":"Zlotnik","year":"2012","journal-title":"Immunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1146\/annurev.pharmtox.42.091901.115838","article-title":"Structure, function, and inhibition of chemokines","volume":"42","author":"Fernandez","year":"2002","journal-title":"Ann. Rev. Pharmacol. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.canlet.2008.04.050","article-title":"The role of CXC chemokines and their receptors in cancer","volume":"267","author":"Vandercappellen","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nri1964","article-title":"Tuning inflammation and immunity by chemokine sequestration: Decoys and more","volume":"6","author":"Mantovani","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1182\/blood.V55.6.931.931","article-title":"The regulation of hemopoiesis in long-term bone marrow cultures. II. Stimulation and inhibition of stem cell proliferation","volume":"55","author":"Toksoz","year":"1980","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/344442a0","article-title":"Identification and characterization of an inhibitor of haemopoietic stem cell proliferation","volume":"344","author":"Graham","year":"1990","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1182\/blood.V76.6.1110.1110","article-title":"Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells","volume":"76","author":"Broxmeyer","year":"1990","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1182\/blood.V79.10.2605.bloodjournal79102605","article-title":"Macrophage-inflammatory protein protects multipotent hematopoietic cells from the cytotoxic effects of hydroxyurea in vivo","volume":"79","author":"Lord","year":"1992","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1084\/jem.179.2.643","article-title":"Macrophage inflammatory protein 1\u03b1, interleukin 3 and diffusible marrow stromal factors maintain human hematopoietic stem cells for at least eight weeks in vitro","volume":"179","author":"Verfaillie","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1084\/jem.170.5.1583","article-title":"Myelopoietic enhancing effects of murine macrophage inflammatory proteins 1 and 2 on colony formation in vitro by murine and human bone marrow granulocyte\/macrophage progenitor cells","volume":"170","author":"Broxmeyer","year":"1989","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1182\/blood-2015-10-673087","article-title":"MIP-1\u03b1\/CCL3-expressing basophil-lineage cells drive the leukemic hematopoiesis of chronic myeloid leukemia in mice","volume":"127","author":"Baba","year":"2016","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.4049\/jimmunol.150.8.3448","article-title":"Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression","volume":"150","author":"Broxmeyer","year":"1993","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/S0301-472X(99)00045-4","article-title":"Regulation of hematopoiesis in a sea of chemokine family members with a plethora of redundant activities","volume":"27","author":"Broxmeyer","year":"1999","journal-title":"Exp. Hematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1182\/blood-2003-05-1595","article-title":"Current mechanistic scenarios in hematopoietic stem\/progenitor cell mobilization","volume":"103","author":"Papayannopoulou","year":"2004","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1182\/blood.V85.12.3412.bloodjournal85123412","article-title":"Mobilization of early hematopoietic progenitor cells with BB-10010: A genetically engineered variant of human macrophage inflammatory protein-1\u03b1","volume":"85","author":"Lord","year":"1995","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1084\/jem.189.12.1987","article-title":"Dominant myelopoietic effector functions mediated by chemokine receptor CCR1","volume":"189","author":"Broxmeyer","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1182\/blood.V85.8.2269.bloodjournal8582269","article-title":"Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability","volume":"85","author":"Laterveer","year":"1995","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1182\/blood.V87.2.781.bloodjournal872781","article-title":"Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8","volume":"87","author":"Laterveer","year":"1996","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/jlb.62.4.503","article-title":"Enhanced mobilization of hematopoietic progenitor cells by mouse MIP-2 and granulocyte colony-stimulating factor in mice","volume":"62","author":"Wang","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1182\/blood-2003-04-1115","article-title":"Neutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GRO\u03b2\/CXCL2 and GRO\u03b2T\/CXCL2\u03944","volume":"103","author":"Pelus","year":"2004","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/jlb.60.3.372","article-title":"Detection of mouse IL-8 receptor homologue expression on peripheral blood leukocytes and mature myeloid lineage cells in bone marrow","volume":"60","author":"Wang","year":"1996","journal-title":"J. Leukoc. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.exphem.2004.11.008","article-title":"The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor","volume":"33","author":"Pelus","year":"2005","journal-title":"Exp. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1084\/jem.20041385","article-title":"Rapid mobilization of murine and human hematopoietic stem and progenitor cells with amd3100, a CXCR4 antagonist","volume":"201","author":"Broxmeyer","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3389\/fimmu.2015.00279","article-title":"The duffy antigen receptor for chemokines DARC\/ACKR1","volume":"6","author":"Horuk","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1182\/blood-2011-11-391730","article-title":"Rantes\/ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing","volume":"119","author":"Ergen","year":"2012","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/ni.3763","article-title":"Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis","volume":"18","author":"Duchene","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/S0140-6736(13)62120-0","article-title":"Chronic myeloid leukaemia","volume":"385","author":"Apperley","year":"2015","journal-title":"Lancet"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1182\/blood.V96.10.3343","article-title":"The molecular biology of chronic myeloid leukemia","volume":"96","author":"Deininger","year":"2000","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1470-2045(10)70233-3","article-title":"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","volume":"11","author":"Mahon","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1182\/blood-2016-09-696013","article-title":"The chronic myeloid leukemia stem cell: Stemming the tide of persistence","volume":"129","author":"Holyoake","year":"2017","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nature08734","article-title":"TGF-\u03b2-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia","volume":"463","author":"Naka","year":"2010","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1073\/pnas.1317072111","article-title":"The ecology in the hematopoietic stem cell niche determines the clinical outcome in chronic myeloid leukemia","volume":"111","author":"MacLean","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1038\/nm.3364","article-title":"Differential regulation of myeloid leukemias by the bone marrow microenvironment","volume":"19","author":"Krause","year":"2013","journal-title":"Nat. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1182\/blood-2013-05-501460","article-title":"Primitive CML cell expansion relies on abnormal levels of BMPS provided by the niche and on BMPRIb overexpression","volume":"122","author":"Laperrousaz","year":"2013","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1182\/blood-2013-11-538694","article-title":"Selectins and their ligands are required for homing and engraftment of BCR-ABL1+ leukemic stem cells in the bone marrow niche","volume":"123","author":"Krause","year":"2014","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.ccr.2012.02.018","article-title":"Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia","volume":"21","author":"Zhang","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/1476-4598-13-169","article-title":"Exosomal shuttling of MIR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells","volume":"13","author":"Taverna","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1182\/blood-2013-10-536078","article-title":"Dipeptidylpeptidase iv (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia","volume":"123","author":"Herrmann","year":"2014","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/sj.leu.2401875","article-title":"Biological effects of stroma-derived factor-1\u03b1 on normal and CML CD34+ haemopoietic cells","volume":"14","author":"Durig","year":"2000","journal-title":"Leukemia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1634\/stemcells.20-3-259","article-title":"Immature leukemic CD34+CXCR4+ cells from CML patients have lower integrin-dependent migration and adhesion in response to the chemokine SDF-1","volume":"20","author":"Peled","year":"2002","journal-title":"Stem Cells"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5313","DOI":"10.1038\/sj.onc.1208596","article-title":"Distinct molecular phenotype of malignant CD34+ hematopoietic stem and progenitor cells in chronic myelogenous leukemia","volume":"24","author":"Kronenwett","year":"2005","journal-title":"Oncogene"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4105","DOI":"10.1038\/onc.2009.260","article-title":"p210(BCR-ABL) desensitizes CDC42 gtpase signaling for SDF-1\u03b1-directed migration in chronic myeloid leukemia cells","volume":"28","author":"Chang","year":"2009","journal-title":"Oncogene"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/S1470-2045(07)70342-X","article-title":"Part I: Mechanisms of resistance to imatinib in chronic myeloid leukaemia","volume":"8","author":"Apperley","year":"2007","journal-title":"Lancet Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1158\/1535-7163.MCT-07-0042","article-title":"CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells","volume":"7","author":"Jin","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/leu.2011.291","article-title":"Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn\/CXCR4 interactions in lipid rafts","volume":"26","author":"Tabe","year":"2012","journal-title":"Leukemia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/leu.2011.360","article-title":"Inhibition of CXCR4 in CML cells disrupts their interaction with the bone marrow microenvironment and sensitizes them to nilotinib","volume":"26","author":"Weisberg","year":"2012","journal-title":"Leukemia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bcp.2014.05.007","article-title":"CXCL12\/CXCR4 axis confers adriamycin resistance to human chronic myelogenous leukemia and oroxylin A improves the sensitivity of K562\/ADM cells","volume":"90","author":"Wang","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1158\/1535-7163.MCT-13-0410","article-title":"Combination of imatinib with CXCR4 antagonist BKT140 overcomes the protective effect of stroma and targets CML in vitro and in vivo","volume":"13","author":"Beider","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/PAT.0000000000000180","article-title":"Expression of multidrug resistance 1 gene in association with CXCL12 in chronic myelogenous leukaemia","volume":"46","author":"Onishi","year":"2014","journal-title":"Pathology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1182\/blood-2011-05-355396","article-title":"Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML","volume":"120","author":"Agarwal","year":"2012","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/stem.5530110925","article-title":"Contrasting effects of rh-MIP-1\u03b1 and TGF-\u03b2 1 on chronic myeloid leukemia progenitors in vitro","volume":"11","author":"Holyoake","year":"1993","journal-title":"Stem Cells"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/stem.5530110924","article-title":"Biological strategies for the selective manipulation of normal and leukemic stem cells","volume":"11","author":"Eaves","year":"1993","journal-title":"Stem Cells"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12015","DOI":"10.1073\/pnas.90.24.12015","article-title":"Unresponsiveness of primitive chronic myeloid leukemia cells to macrophage inflammatory protein 1\u03b1, an inhibitor of primitive normal hematopoietic cells","volume":"90","author":"Eaves","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6191","DOI":"10.4049\/jimmunol.162.10.6191","article-title":"Macrophage-inflammatory protein-1\u03b1 receptor expression on normal and chronic myeloid leukemia CD34+ cells","volume":"162","author":"Nicholls","year":"1999","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1182\/blood.V86.11.4270.bloodjournal86114270","article-title":"Macrophage inflammatory protein-1\u03b1 receptors are present on cells enriched for CD34 expression from patients with chronic myeloid leukemia","volume":"86","author":"Chasty","year":"1995","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1038\/sj.leu.2401610","article-title":"Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1\u03b1","volume":"13","author":"Durig","year":"1999","journal-title":"Leukemia"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1084\/jem.20130112","article-title":"MIP-1\u03b1\/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia","volume":"210","author":"Baba","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/sj.onc.1201914","article-title":"ABL protein kinase abrogates the response of multipotent haemopoietic cells to the growth inhibitor macrophage inflammatory protein-1\u03b1","volume":"16","author":"Wark","year":"1998","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1182\/blood.V92.10.3780","article-title":"Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving p210 BCR\/ABL-transduced bone marrow","volume":"92","author":"Pear","year":"1998","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1182\/blood-2003-12-4369","article-title":"Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis","volume":"105","author":"Koschmieder","year":"2005","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/jhg.2015.114","article-title":"Recent advances in rasopathies","volume":"61","author":"Aoki","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nature20131","article-title":"Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment","volume":"539","author":"Dong","year":"2016","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.molonc.2008.07.003","article-title":"The chemokine interleukin-8 and the surface activation protein CD69 are markers for BCR-ABL activity in chronic myeloid leukemia","volume":"2","author":"Hantschel","year":"2008","journal-title":"Mol. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.canlet.2014.03.009","article-title":"Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells","volume":"348","author":"Corrado","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1182\/blood.V92.7.2338","article-title":"MCP-1, not MIP-1\u03b1, is the endogenous chemokine that cooperates with TGF-\u03b2 to inhibit the cycling of primitive normal but not leukemic (CML) progenitors in long-term human marrow cultures","volume":"92","author":"Cashman","year":"1998","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"715","DOI":"10.18632\/oncotarget.990","article-title":"Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations","volume":"4","author":"Gerber","year":"2013","journal-title":"Oncotarget"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/sj.leu.2403626","article-title":"BCR\/ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR\/ABL-positive cells","volume":"19","author":"Salesse","year":"2005","journal-title":"Leukemia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.bbrc.2015.06.020","article-title":"CCR7 is involved in BCR-ABL\/stap-2-mediated cell growth in hematopoietic Ba\/F3 cells","volume":"463","author":"Kubo","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1182\/blood.V95.4.1506.004k41_1506_1508","article-title":"The exodus subfamily of CC chemokines inhibits the proliferation of chronic myelogenous leukemia progenitors","volume":"95","author":"Hromas","year":"2000","journal-title":"Blood"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1824\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:42:58Z","timestamp":1760208178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,22]]},"references-count":101,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["ijms18081824"],"URL":"https:\/\/doi.org\/10.3390\/ijms18081824","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,22]]}}}