{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T22:15:36Z","timestamp":1758406536654,"version":"3.37.3"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001318","name":"University of the West of England","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001318","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tumour microenvironments are hallmarked in many cancer types. In haematological malignancies, bone marrow (BM) mesenchymal stromal cells (MSC) protect malignant cells from drug-induced cytotoxicity. However, less is known about malignant impact on supportive stroma. Notably, it is unknown whether these interactions alter long-term genotoxic damage in either direction. The nucleoside analogue cytarabine (ara-C), common in haematological therapies, remains the most effective agent for acute myeloid leukaemia, yet one-third of patients develop resistance. This study aimed to evaluate the bidirectional effect of MSC and malignant cell co-culture on ara-C genotoxicity modulation. Primary MSC, isolated from patient BM aspirates for haematological investigations, and malignant haematopoietic cells (leukaemic HL-60) were co-cultured using trans-well inserts, prior to treatment with physiological dose ara-C. Co-culture genotoxic effects were assessed by micronucleus and alkaline comet assays. Patient BM cells from chemotherapy-treated patients had reduced ex vivo survival (P = 0.0049) and increased genotoxicity (P = 0.3172) than untreated patients. It was shown for the first time that HL-60 were protected by MSC from ara-C-induced genotoxicity, with reduced MN incidence in co-culture as compared to mono-culture (P = 0.0068). Comet tail intensity also significantly increased in ara-C-treated MSC with HL-60 influence (P = 0.0308). MSC sensitisation to ara-C genotoxicity was also demonstrated following co-culture with HL60 (P = 0.0116), which showed significantly greater sensitisation when MSC-HL-60 co-cultures were exposed to ara-C (P = 0.0409). This study shows for the first time that malignant HSC and MSC bidirectionally modulate genotoxicity, providing grounding for future research identifying mechanisms of altered genotoxicity in leukaemic microenvironments. MSC retain long-term genotoxic and functional damage following chemotherapy exposure. Understanding the interactions perpetuating such damage may inform modifications to reduce therapy-related complications, such as secondary malignancies and BM failure.<\/jats:p>","DOI":"10.1093\/mutage\/geab033","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T03:14:15Z","timestamp":1631243655000},"page":"419-428","source":"Crossref","is-referenced-by-count":11,"title":["Primary mesenchymal stromal cells in co-culture with leukaemic HL-60 cells are sensitised to cytarabine-induced genotoxicity, while leukaemic cells are protected"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-359X","authenticated-orcid":false,"given":"Liana E","family":"Gynn","sequence":"first","affiliation":[{"name":"Centre for Research in Biosciences, Department of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Anderson","sequence":"additional","affiliation":[{"name":"Centre for Research in Biosciences, Department of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth","family":"Robinson","sequence":"additional","affiliation":[{"name":"Centre for Research in Biosciences, Department of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah A","family":"Wexler","sequence":"additional","affiliation":[{"name":"Department of Oncology\/Haematology, Royal United Hospitals Bath NHS Foundation Trust, Bath BA1 3NG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Upstill-Goddard","sequence":"additional","affiliation":[{"name":"Department of Oncology\/Haematology, Royal United Hospitals Bath NHS Foundation Trust, Bath BA1 3NG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Oncology\/Haematology, Royal United Hospitals Bath NHS Foundation Trust, Bath BA1 3NG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-2551","authenticated-orcid":false,"given":"Jennifer E","family":"May","sequence":"additional","affiliation":[{"name":"Centre for Research in Biosciences, Department of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"2021120108360268200_CIT0001","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.3324\/haematol.2014.113852","article-title":"A hostel for the hostile: the bone marrow niche in hematologic neoplasms","volume":"100","author":"Krause","year":"2015","journal-title":"Haematologica"},{"key":"2021120108360268200_CIT0002","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.3389\/fonc.2019.01135","article-title":"The yin and yang of the bone marrow microenvironment: pros and cons of mesenchymal stromal cells in acute myeloid leukemia","volume":"9","author":"Ciciarello","year":"2019","journal-title":"Front. Oncol."},{"key":"2021120108360268200_CIT0003","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11912-020-0885-0","article-title":"Acute myeloid leukaemia in its niche: the bone marrow microenvironment in acute myeloid leukaemia","volume":"22","author":"Ladikou","year":"2020","journal-title":"Curr. Oncol. Rep."},{"key":"2021120108360268200_CIT0004","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.stem.2015.02.019","article-title":"Mesenchymal cell contributions to the stem cell niche","volume":"16","author":"Kfoury","year":"2015","journal-title":"Cell Stem Cell"},{"key":"2021120108360268200_CIT0005","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nrclinonc.2011.31","article-title":"The bone marrow stroma in hematological neoplasms \u2013 a guilty bystander","volume":"8","author":"Tripodo","year":"2011","journal-title":"Nat Rev Clin Oncol."},{"key":"2021120108360268200_CIT0006","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s11899-015-0253-6","article-title":"Role of microenvironment in resistance to therapy in AML","volume":"10","author":"Tabe","year":"2015","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"2021120108360268200_CIT0007","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":"2021120108360268200_CIT0008","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41568-020-0245-2","article-title":"Bone marrow niches in haematological malignancies","volume":"20","author":"M\u00e9ndez-Ferrer","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"2021120108360268200_CIT0009","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1056\/NEJMoa1112304","article-title":"Prognostic relevance of integrated genetic profiling in acute myeloid leukemia","volume":"366","author":"Patel","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2021120108360268200_CIT0010","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.blre.2017.03.004","article-title":"The bone marrow microenvironment\u2014home of the leukemic blasts","volume":"31","author":"Shafat","year":"2017","journal-title":"Blood Rev."},{"key":"2021120108360268200_CIT0011","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"2021120108360268200_CIT0012","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41556-019-0444-9","article-title":"Dynamic responses of the haematopoietic stem cell niche to diverse stresses","volume":"22","author":"Batsivari","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"2021120108360268200_CIT0013","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/1479-5876-11-298","article-title":"Leukemia cells induce changes in human bone marrow stromal cells","volume":"11","author":"Civini","year":"2013","journal-title":"J. Transl. Med."},{"key":"2021120108360268200_CIT0014","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1158\/0008-5472.CAN-14-3379","article-title":"Microenvironmental remodeling as a parameter and prognostic factor of heterogeneous leukemogenesis in acute myelogenous leukemia","volume":"75","author":"Kim","year":"2015","journal-title":"Cancer Res."},{"key":"2021120108360268200_CIT0015","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ccell.2017.08.001","article-title":"Increased vascular permeability in the bone marrow microenvironment contributes to disease progression and drug response in acute myeloid leukemia","volume":"32","author":"Passaro","year":"2017","journal-title":"Cancer Cell"},{"key":"2021120108360268200_CIT0016","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.3390\/ijms19072031","article-title":"New insights in anti-angiogenesis in multiple myeloma","volume":"19","author":"Ribatti","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2021120108360268200_CIT0017","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3390\/ijms21020613","article-title":"Bone marrow stromal cells-induced drug resistance in multiple myeloma","volume":"21","author":"Ria","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2021120108360268200_CIT0018","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.ccr.2014.02.005","article-title":"Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance","volume":"25","author":"Cao","year":"2014","journal-title":"Cancer Cell"},{"key":"2021120108360268200_CIT0019","doi-asserted-by":"crossref","first-page":"904","DOI":"10.3390\/ijms21030904","article-title":"Impact and intricacies of bone marrow microenvironment in b-cell lymphomas: From biology to therapy","volume":"21","author":"Sircar","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2021120108360268200_CIT0020","doi-asserted-by":"crossref","first-page":"e188","DOI":"10.12788\/jcso.0428","article-title":"Effect of time of admission to treatment initiation on outcomes of patients with acute myeloid leukemia: a tertiary care referral center experience","volume":"16","author":"Ibrahimi","year":"2018","journal-title":"J Community Support Oncol."},{"key":"2021120108360268200_CIT0021","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1158\/2159-8290.CD-19-1011","article-title":"Advances in the treatment of acute myeloid leukemia: new drugs and new challenges","volume":"10","author":"Short","year":"2020","journal-title":"Cancer Discov."},{"key":"2021120108360268200_CIT0022","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2217\/pgs.10.191","article-title":"Identification of predictive markers of cytarabine response in AML by integrative analysis of gene-expression profiles with multiple phenotypes","volume":"12","author":"Lamba","year":"2011","journal-title":"Pharmacogenomics"},{"key":"2021120108360268200_CIT0023","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.bios.2013.09.014","article-title":"Investigation and verification of a bioluminescent biosensor for the quantitation of ara-CTP generation: a biomarker for cytosine arabinoside sensitivity in acute myeloid leukaemia","volume":"52","author":"Anderson","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"2021120108360268200_CIT0024","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0027-5107(85)90183-6","article-title":"Cytosine arabinoside is a potent clastogen and does not affect the repair of X-ray-induced chromosome fragments in unstimulated human lymphocytes","volume":"151","author":"Pantelias","year":"1985","journal-title":"Mutat. Res."},{"key":"2021120108360268200_CIT0025","doi-asserted-by":"crossref","first-page":"e151","DOI":"10.1097\/HS9.0000000000000151","article-title":"Mesenchymal stromal cells: role in the BM niche and in the support of hematopoietic stem cell transplantation","volume":"2","author":"Crippa","year":"2018","journal-title":"Hemasphere"},{"key":"2021120108360268200_CIT0026","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.1182\/blood.V126.23.4353.4353","article-title":"High incidence of secondary malignancies after reduced intensity Allo-SCT: results of a single-center study with extended follow-up","volume":"126","author":"Delage","year":"2015","journal-title":"Blood"},{"key":"2021120108360268200_CIT0027","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0140-6736(98)11079-6","article-title":"High incidence of secondary brain tumours after radiotherapy and antimetabolites","volume":"354","author":"Relling","year":"1999","journal-title":"Lancet"},{"key":"2021120108360268200_CIT0028","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/bmt.2014.325","article-title":"Secondary malignancies following high dose therapy and autologous hematopoietic cell transplantation-systematic review and meta-analysis","volume":"50","author":"Vaxman","year":"2015","journal-title":"Bone Marrow Transplant"},{"key":"2021120108360268200_CIT0029","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/bjh.16090","article-title":"Risk of secondary haematological malignancies in patients with follicular lymphoma: an analysis of 1028 patients treated in the rituximab era","volume":"187","author":"Prusila","year":"2019","journal-title":"Br. J. Haematol."},{"key":"2021120108360268200_CIT0030","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.21873\/anticanres.13600","article-title":"Chronic myeloid leukemia as secondary malignancy following the treatment of Hodgkin lymphoma: a case series","volume":"39","author":"Millett","year":"2019","journal-title":"Anticancer Res."},{"key":"2021120108360268200_CIT0031","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/00129804-200311000-00004","article-title":"Chemotherapy-induced secondary malignancies","volume":"26","author":"Vega-Stromberg","year":"2003","journal-title":"J. Infus. Nurs."},{"key":"2021120108360268200_CIT0032","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1200\/JCO.2010.28.9777","article-title":"Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma","volume":"29","author":"Tarella","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"2021120108360268200_CIT0033","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s00277-010-1141-8","article-title":"Alkylating chemotherapeutic agents cyclophosphamide and melphalan cause functional injury to human bone marrow-derived mesenchymal stem cells","volume":"90","author":"Kemp","year":"2011","journal-title":"Ann. Hematol."},{"key":"2021120108360268200_CIT0034","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/mutage\/gey014","article-title":"Chemotherapy-induced genotoxic damage to bone marrow cells: long-term implications","volume":"33","author":"May","year":"2018","journal-title":"Mutagenesis"},{"key":"2021120108360268200_CIT0035","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.exphem.2005.02.004","article-title":"Mesenchymal stem cells remain of host origin even a long time after allogeneic peripheral blood stem cell or bone marrow transplantation","volume":"33","author":"Rieger","year":"2005","journal-title":"Exp. Hematol."},{"key":"2021120108360268200_CIT0036","doi-asserted-by":"crossref","first-page":"e0169921","DOI":"10.1371\/journal.pone.0169921","article-title":"Resistance for genotoxic damage in mesenchymal stromal cells is increased by hypoxia but not generally dependent on p53-regulated cell cycle arrest","volume":"12","author":"L\u00fctzkendorf","year":"2017","journal-title":"PLoS One"},{"key":"2021120108360268200_CIT0037","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"2021120108360268200_CIT0038","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/S0301-472X(01)00612-9","article-title":"Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5)","volume":"29","author":"Garrido","year":"2001","journal-title":"Exp. Hematol."},{"key":"2021120108360268200_CIT0039","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1038\/sj.leu.2402608","article-title":"Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins","volume":"16","author":"Konopleva","year":"2002","journal-title":"Leukemia"},{"key":"2021120108360268200_CIT0040","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1080\/10428190701593636","article-title":"Chemotherapeutic treatment of bone marrow stromal cells strongly affects their protective effect on acute myeloid leukemia cell survival","volume":"49","author":"Moshaver","year":"2008","journal-title":"Leuk. Lymphoma"},{"key":"2021120108360268200_CIT0041","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fimmu.2017.00106","article-title":"Mesenchymal stem cells support survival and proliferation of primary human acute myeloid leukemia cells through heterogeneous molecular mechanisms","volume":"8","author":"Brenner","year":"2017","journal-title":"Front. Immunol."},{"key":"2021120108360268200_CIT0042","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/bjh.13492","article-title":"Stromal CYR61 confers resistance to mitoxantrone via spleen tyrosine kinase activation in human acute myeloid leukaemia","volume":"170","author":"Long","year":"2015","journal-title":"Br. J. Haematol."},{"key":"2021120108360268200_CIT0043","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1158\/0008-5472.CAN-16-1095","article-title":"MIF-induced stromal PKC\u03b2\/IL8 is essential in human acute myeloid leukemia","volume":"77","author":"Abdul-Aziz","year":"2017","journal-title":"Cancer Res."},{"key":"2021120108360268200_CIT0044","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12929-018-0407-7","article-title":"Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs","volume":"25","author":"Somaiah","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"2021120108360268200_CIT0045","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"2021120108360268200_CIT0046","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.leukres.2013.02.012","article-title":"A novel bioluminescent bacterial biosensor for measurement of Ara-CTP and cytarabine potentiation by fludarabine in seven leukaemic cell lines","volume":"37","author":"Anderson","year":"2013","journal-title":"Leuk. Res."},{"key":"2021120108360268200_CIT0047","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.clml.2014.08.006","article-title":"Progress in acute myeloid leukemia","volume":"15","author":"Kadia","year":"2015","journal-title":"Clin. Lymphoma. Myeloma Leuk."},{"key":"2021120108360268200_CIT0048","first-page":"1","volume-title":"OECD Guideline for the Testing of Chemicals: In Vitro Mammalian Cell Micronucleus Test (TG 487)","author":"OECD","year":"2014"},{"key":"2021120108360268200_CIT0049","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.mrgentox.2008.06.004","article-title":"Comparison of different methods for an accurate assessment of cytotoxicity in the in vitro micronucleus test. II: Practical aspects with toxic agents","volume":"655","author":"Fellows","year":"2008","journal-title":"Mutat. Res."},{"key":"2021120108360268200_CIT0050","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1038\/s41596-020-0398-1","article-title":"Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results","volume":"15","author":"M\u00f8ller","year":"2020","journal-title":"Nat. Protoc."},{"key":"2021120108360268200_CIT0051","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1093\/mutage\/gen015","article-title":"Statistical issues in the use of the comet assay","volume":"23","author":"Lovell","year":"2008","journal-title":"Mutagenesis"},{"key":"2021120108360268200_CIT0052","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1787\/9789264264885-en","volume-title":"OECD Guideline for the Testing of Chemicals: In Vivo Mammalian Alkaline Comet Assay (TG 489)","author":"OECD","year":"2016"},{"key":"2021120108360268200_CIT0053","doi-asserted-by":"crossref","first-page":"23073","DOI":"10.18632\/oncotarget.14981","article-title":"Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome","volume":"8","author":"Macanas-Pirard","year":"2017","journal-title":"Oncotarget"},{"key":"2021120108360268200_CIT0054","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrgentox.2008.06.003","article-title":"Comparison of different methods for an accurate assessment of cytotoxicity in the in vitro micronucleus test. I. Theoretical aspects","volume":"655","author":"Lorge","year":"2008","journal-title":"Mutat. Res."},{"key":"2021120108360268200_CIT0055","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/mutage\/gep060","article-title":"Combining the in vivo comet and micronucleus assays: a practical approach to genotoxicity testing and data interpretation","volume":"25","author":"Vasquez","year":"2010","journal-title":"Mutagenesis"},{"key":"2021120108360268200_CIT0056","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/leu.2012.299","article-title":"Secondary malignancies after allogeneic stem-cell transplantation in the era of reduced-intensity conditioning; the incidence is not reduced","volume":"27","author":"Shimoni","year":"2013","journal-title":"Leukemia"},{"issue":"11","key":"2021120108360268200_CIT0057","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.bbmt.2014.07.009","article-title":"Second solid cancers after allogeneic hematopoietic cell transplantation using reduced intensity conditioning","volume":"20","author":"Ringd\u00e9n","year":"2014","journal-title":"Biol. Blood Marrow Transpl."},{"key":"2021120108360268200_CIT0058","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1007\/s00018-017-2725-4","article-title":"Role of the microenvironment in myeloid malignancies","volume":"75","author":"Goulard","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"2021120108360268200_CIT0059","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1590\/1678-4685-GMB-2015-0057","article-title":"Human mesenchymal stem cells are resistant to cytotoxic and genotoxic effects of cisplatin in vitro","volume":"39","author":"Bellagamba","year":"2016","journal-title":"Genet. Mol. Biol."},{"key":"2021120108360268200_CIT0060","doi-asserted-by":"crossref","first-page":"101536","DOI":"10.1016\/j.scr.2019.101536","article-title":"Mesenchymal stem cells preserve their stem cell traits after exposure to antimetabolite chemotherapy","volume":"40","author":"Lopez Perez","year":"2019","journal-title":"Stem Cell Res."},{"key":"2021120108360268200_CIT0061","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1532\/IJH97.A10505","article-title":"Mesenchymal stem cells in stem cell transplant recipients are damaged and remain of host origin","volume":"82","author":"Wang","year":"2005","journal-title":"Int. J. Hematol."},{"key":"2021120108360268200_CIT0062","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1365-2141.2004.05200.x","article-title":"Differential damage and recovery of human mesenchymal stem cells after exposure to chemotherapeutic agents","volume":"127","author":"Li","year":"2004","journal-title":"Br. J. Haematol."},{"key":"2021120108360268200_CIT0063","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s00277-009-0896-2","article-title":"Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy","volume":"89","author":"Kemp","year":"2010","journal-title":"Ann. Hematol."},{"key":"2021120108360268200_CIT0064","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1080\/10428194.2016.1187277","article-title":"Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation","volume":"58","author":"Shipounova","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"2021120108360268200_CIT0065","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/s12185-017-2300-7","article-title":"The DNA damage response pathway in normal hematopoiesis and malignancies","volume":"106","author":"Delia","year":"2017","journal-title":"Int. J. Hematol."},{"key":"2021120108360268200_CIT0066","doi-asserted-by":"crossref","first-page":"299","DOI":"10.15171\/apb.2015.042","article-title":"The impact of mesenchymal stem cells on differentiation of hematopoietic stem cells","volume":"5","author":"Saleh","year":"2015","journal-title":"Adv. Pharm. Bull."},{"key":"2021120108360268200_CIT0067","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fbioe.2016.00012","article-title":"In vitro tumor models: advantages, disadvantages, variables, and selecting the right platform","volume":"4","author":"Katt","year":"2016","journal-title":"Front. Bioeng. Biotechnol."},{"key":"2021120108360268200_CIT0068","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0140-6736(18)31041-9","article-title":"Acute myeloid leukaemia","volume":"392","author":"Short","year":"2018","journal-title":"Lancet"},{"key":"2021120108360268200_CIT0069","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/mutage\/9.3.273","article-title":"The origin of micronuclei induced by cytosine arabinoside and its synergistic interaction with hydroxyurea in human lymphocytes","volume":"9","author":"Fenech","year":"1994","journal-title":"Mutagenesis"},{"key":"2021120108360268200_CIT0070","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1093\/toxsci\/kfu058","article-title":"Chromosome breakage induced by the genotoxic agents mitomycin C and cytosine arabinoside is concentration and p53 dependent","volume":"140","author":"Br\u00fcsehafer","year":"2014","journal-title":"Toxicol. Sci."},{"key":"2021120108360268200_CIT0071","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10565-007-9042-x","article-title":"Detection of excision repaired DNA damage in the comet assay by using Ara-C and hydroxyurea in three different cell types","volume":"25","author":"G\u00fcerci","year":"2009","journal-title":"Cell Biol. Toxicol."},{"key":"2021120108360268200_CIT0072","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/mutage\/geu053","article-title":"Abstracts of the 43rd Annual Meeting of the European Environmental Mutagen Society Lancaster University UK 6\u201310 July 2014","volume":"29","author":"Andrews","year":"2014","journal-title":"Mutagenesis"},{"key":"2021120108360268200_CIT0073","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1080\/10428194.2017.1413188","article-title":"DNA damage response-initiated cytokine secretion in bone marrow stromal cells promotes chemoresistance of myeloma cells","volume":"59","author":"Tang","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"2021120108360268200_CIT0074","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/sj.leu.2402022","article-title":"The bone marrow stromal microenvironment influences myeloma therapeutic response in vitro","volume":"15","author":"Cheung","year":"2001","journal-title":"Leukemia"},{"key":"2021120108360268200_CIT0075","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrclinonc.2017.197","article-title":"The bone-marrow niche in MDS and MGUS: implications for AML and MM","volume":"15","author":"Ghobrial","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2021120108360268200_CIT0076","doi-asserted-by":"crossref","first-page":"e0213452","DOI":"10.1371\/journal.pone.0213452","article-title":"Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis","volume":"14","author":"Rennerfeldt","year":"2019","journal-title":"PLoS One"},{"key":"2021120108360268200_CIT0077","doi-asserted-by":"crossref","first-page":"10494","DOI":"10.1073\/pnas.1902375116","article-title":"Heterogeneity in refractory acute myeloid leukemia","volume":"116","author":"Horibata","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021120108360268200_CIT0078","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1089\/scd.2007.0008","article-title":"Phenotypic and functional comparison of mesenchymal stem cells derived from the bone marrow of normal adults and patients with hematologic malignant diseases","volume":"16","author":"Zhao","year":"2007","journal-title":"Stem Cells Dev."},{"key":"2021120108360268200_CIT0079","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/14728222.2017.1300255","article-title":"Patients with acute myeloid leukemia can be subclassified based on the constitutive cytokine release of the leukemic cells; the possible clinical relevance and the importance of cellular iron metabolism","volume":"21","author":"Brenner","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"2021120108360268200_CIT0080","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"D\u00f6hner","year":"2017","journal-title":"Blood"}],"container-title":["Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mutage\/advance-article-pdf\/doi\/10.1093\/mutage\/geab033\/40482137\/geab033.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mutage\/article-pdf\/36\/6\/419\/41377420\/geab033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mutage\/article-pdf\/36\/6\/419\/41377420\/geab033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T13:30:30Z","timestamp":1638365430000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mutage\/article\/36\/6\/419\/6368295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,10]]},"references-count":80,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,9,10]]},"published-print":{"date-parts":[[2021,11,29]]}},"URL":"https:\/\/doi.org\/10.1093\/mutage\/geab033","relation":{},"ISSN":["0267-8357","1464-3804"],"issn-type":[{"type":"print","value":"0267-8357"},{"type":"electronic","value":"1464-3804"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,9,10]]}}}