{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T13:57:05Z","timestamp":1695563825879},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,9,26]],"date-time":"2012-09-26T00:00:00Z","timestamp":1348617600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>-<\/jats:sup> subset of AML cells is enriched for resistance to current chemotherapeutic agents and considered to contribute to disease progression and relapse in Acute Myeloid Leukaemia (AML) patients following initial treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Chemosensitivity in phenotypically defined subsets from 34 primary AML samples was measured by flow cytometry following 48\u2009hr <jats:italic>in vitro<\/jats:italic> treatment with gemtuzumab ozogamicin (GO, Mylotarg) and the farnesyltransferase inhibitor tipifarnib\/zarnestra. The DNA damage response was measured using flow cytometry, immunofluorescence and immunohistochemistry.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Using a previously validated <jats:italic>in vitro<\/jats:italic> minimal residual disease model, we now show that the combination of GO (10\u2009ng\/ml) and tipifarnib (5\u2009\u03bcM) targets the CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>-<\/jats:sup> subset resulting in 65% median cell loss compared to 28% and 13% CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>-<\/jats:sup> cell loss in GO-treated and tipifarnib-treated cells, respectively. Using phosphokinome profiling and immunofluorescence in the TF-1a cell line, we demonstrate that the drug combination is characterised by the activation of a DNA damage response (induction of \u03b3H2A.X and thr68 phosphorylation of chk2). Higher induction of \u03b3H2AX was found in CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>-<\/jats:sup> than in CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>+<\/jats:sup> patient cells. In a model system, we show that dormancy impairs damage resolution, allowing accumulation of \u03b3H2AX foci.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The chemosensitivity of the CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>-<\/jats:sup> subset, combined with enhanced damage indicators, suggest that this subset is primed to favour programmed cell death as opposed to repairing damage. This interaction between tipifarnib and GO suggests a potential role in the treatment of AML.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-12-431","type":"journal-article","created":{"date-parts":[[2012,9,27]],"date-time":"2012-09-27T14:48:22Z","timestamp":1348757302000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeting of CD34+CD38-cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia"],"prefix":"10.1186","volume":"12","author":[{"given":"Mays","family":"Jawad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Seedhouse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karuna","family":"Tandon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel H","family":"Russell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Pallis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,9,26]]},"reference":[{"key":"3331_CR1","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/nm0797-730","volume":"3","author":"D Bonnet","year":"1997","unstructured":"Bonnet D, Dick JE: Human acute leukemia is organised as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997, 3: 730-737. 10.1038\/nm0797-730.","journal-title":"Nat Med"},{"issue":"1","key":"3331_CR2","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ccr.2010.12.012","volume":"19","author":"N Goardon","year":"2011","unstructured":"Goardon N, Marchi E, Atzberger A, Quek L, Schuh A, Soneji S, Woll P, Mead A, Alford KA, Rout R, et al: Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell. 2011, 19 (1): 138-152. 10.1016\/j.ccr.2010.12.012.","journal-title":"Cancer Cell"},{"issue":"9","key":"3331_CR3","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1038\/nm.2415","volume":"17","author":"K Eppert","year":"2011","unstructured":"Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, van Galen P, Metzeler KH, Poeppl A, Ling V, Beyene J, et al: Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med. 2011, 17 (9): 1086-1093. 10.1038\/nm.2415.","journal-title":"Nat Med"},{"key":"3331_CR4","doi-asserted-by":"publisher","first-page":"16220","DOI":"10.1073\/pnas.252462599","volume":"99","author":"ML Guzman","year":"2002","unstructured":"Guzman ML, Swiderski CF, Howard DS, Grimes BA, Rossi RM, Szilvassy SJ, Jordan CT: Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci U S A. 2002, 99: 16220-16225. 10.1073\/pnas.252462599.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"16","key":"3331_CR5","first-page":"4403","volume":"60","author":"RT Costello","year":"2000","unstructured":"Costello RT, Mallet F, Gaugler B, Sainty D, Arnoulet C, Gastaut JA, Olive D: Human acute myeloid leukemia CD34+\/CD38- progenitor cells have decreased sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities. Cancer Res. 2000, 60 (16): 4403-4411.","journal-title":"Cancer Res"},{"issue":"18","key":"3331_CR6","doi-asserted-by":"publisher","first-page":"6520","DOI":"10.1158\/1078-0432.CCR-05-0468","volume":"11","author":"A van Rhenen","year":"2005","unstructured":"van Rhenen A, Feller N, Kelder A, Westra AH, Rombouts E, Zweegman S, van der Pol MA, Waisfisz Q, Ossenkoppele GJ, Schuurhuis GJ: High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin Cancer Res. 2005, 11 (18): 6520-6527. 10.1158\/1078-0432.CCR-05-0468.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"3331_CR7","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1200\/JCO.2010.31.4310","volume":"29","author":"AK Burnett","year":"2011","unstructured":"Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K: Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011, 29 (4): 369-377. 10.1200\/JCO.2010.31.4310.","journal-title":"J Clin Oncol"},{"key":"3331_CR8","first-page":"326","volume":"114","author":"S Petersdorf","year":"2009","unstructured":"Petersdorf S, Kopecky K, Stuart R, Larson R, Nevill T, Stenke L, Slovak M, Tallman M, Willman C, Erba H, et al: Preliminary results of southwest oncology group study S0106: an international intergroup phase 3 randomized trial comparing the addition of gemtuzumab ozogamicin to standard induction therapy versus standard induction therapy followed by a second randomization to post-consolidation gemtuzumab ozogamicin versus no additional therapy for previously untreated acute myeloid leukemia. Blood (ASH Annual Meeting Abstracts). 2009, 114: 326-","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"issue":"21","key":"3331_CR9","first-page":"582","volume":"118","author":"AK Burnett","year":"2011","unstructured":"Burnett AK, Hills RK, Hunter AE, Milligan D, Kell WJ, Wheatley K, Yin JL, Ali S, Kjeldsen L, Bowen D, et al: The addition of gemtuzumab ozogamicin to intensive chemotherapy in older patients with AML produces a significant improvement in overall survival: results of the UK NCRI AML16 randomized trial. ASH Annual Meeting Abstracts. 2011, 118 (21): 582-","journal-title":"ASH Annual Meeting Abstracts"},{"issue":"9825","key":"3331_CR10","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1016\/S0140-6736(12)60485-1","volume":"379","author":"S Castaigne","year":"2012","unstructured":"Castaigne S, Pautas C, Terre C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, et al: Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012, 379 (9825): 1508-1516. 10.1016\/S0140-6736(12)60485-1.","journal-title":"Lancet"},{"key":"3331_CR11","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/leu.2009.199","volume":"24","author":"M Jawad","year":"2010","unstructured":"Jawad M, Seedhouse C, Mony U, Grundy M, Russell NH, Pallis M: Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia. Leukemia. 2010, 24: 74-80. 10.1038\/leu.2009.199.","journal-title":"Leukemia"},{"issue":"5","key":"3331_CR12","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1182\/blood-2002-07-1973","volume":"101","author":"J Cortes","year":"2003","unstructured":"Cortes J, Albitar M, Thomas D, Giles F, Kurzrock R, Thibault A, Rackoff W, Koller C, O'Brien S, Garcia-Manero G, et al: Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood. 2003, 101 (5): 1692-1697. 10.1182\/blood-2002-07-1973.","journal-title":"Blood"},{"issue":"2","key":"3331_CR13","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1158\/1078-0432.CCR-07-1532","volume":"14","author":"R Kurzrock","year":"2008","unstructured":"Kurzrock R, Kantarjian HM, Blascovich MA, Bucher C, Verstovsek S, Wright JJ, Pilat SR, Cortes JE, Estey EH, Giles FJ, et al: Phase I study of alternate-week administration of tipifarnib in patients with myelodysplastic syndrome. Clin Cancer Res. 2008, 14 (2): 509-514. 10.1158\/1078-0432.CCR-07-1532.","journal-title":"Clin Cancer Res"},{"issue":"10","key":"3331_CR14","doi-asserted-by":"publisher","first-page":"4158","DOI":"10.1182\/blood-2006-07-035725","volume":"109","author":"P Fenaux","year":"2007","unstructured":"Fenaux P, Raza A, Mufti GJ, Aul C, Germing U, Kantarjian H, Cripe L, Kerstens R, De Porre P, Kurzrock R: A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome. Blood. 2007, 109 (10): 4158-4163. 10.1182\/blood-2006-07-035725.","journal-title":"Blood"},{"issue":"4","key":"3331_CR15","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/sj.leu.2404539","volume":"21","author":"BC Medeiros","year":"2007","unstructured":"Medeiros BC, Landau HJ, Morrow M, Lockerbie RO, Pitts T, Eckhardt SG: The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines. Leukemia. 2007, 21 (4): 739-746.","journal-title":"Leukemia"},{"issue":"6","key":"3331_CR16","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1111\/j.1600-0609.2004.00336.x","volume":"73","author":"A Korycka","year":"2004","unstructured":"Korycka A, Smolewski P, Robak T: The influence of farnesyl protein transferase inhibitor R115777 (Zarnestra) alone and in combination with purine nucleoside analogs on acute myeloid leukemia progenitors in vitro. Eur J Haematol. 2004, 73 (6): 418-426. 10.1111\/j.1600-0609.2004.00336.x.","journal-title":"Eur J Haematol"},{"issue":"2","key":"3331_CR17","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1158\/1078-0432.CCR-05-1792","volume":"12","author":"N Yanamandra","year":"2006","unstructured":"Yanamandra N, Colaco NM, Parquet NA, Buzzeo RW, Boulware D, Wright G, Perez LE, Dalton WS, Beaupre DM: Tipifarnib and bortezomib are synergistic and overcome cell adhesion-mediated drug resistance in multiple myeloma and acute myeloid leukemia. Clin Cancer Res. 2006, 12 (2): 591-599. 10.1158\/1078-0432.CCR-05-1792.","journal-title":"Clin Cancer Res"},{"issue":"1","key":"3331_CR18","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1182\/blood-2011-08-370825","volume":"119","author":"JE Karp","year":"2012","unstructured":"Karp JE, Vener TI, Raponi M, Ritchie EK, Smith BD, Gore SD, Morris LE, Feldman EJ, Greer JM, Malek S, et al: Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia. Blood. 2012, 119 (1): 55-63. 10.1182\/blood-2011-08-370825.","journal-title":"Blood"},{"issue":"6","key":"3331_CR19","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1002\/cncr.25575","volume":"117","author":"E Jabbour","year":"2011","unstructured":"Jabbour E, Kantarjian H, Ravandi F, Garcia-Manero G, Estrov Z, Verstovsek S, O'Brien S, Faderl S, Thomas DA, Wright JJ, et al: A phase 1\u20132 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Cancer. 2011, 117 (6): 1236-1244. 10.1002\/cncr.25575.","journal-title":"Cancer"},{"issue":"7","key":"3331_CR20","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1038\/leu.2008.125","volume":"22","author":"U Mony","year":"2008","unstructured":"Mony U, Jawad M, Seedhouse C, Russell N, Pallis M: Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment. Leukemia. 2008, 22 (7): 1395-1401. 10.1038\/leu.2008.125.","journal-title":"Leukemia"},{"issue":"4","key":"3331_CR21","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/(SICI)1097-0320(19991201)37:4<308::AID-CYTO8>3.0.CO;2-Z","volume":"37","author":"M Pallis","year":"1999","unstructured":"Pallis M, Syan J, Russell NH: Flow cytometric chemosensitivity analysis of blasts from patients with acute myeloblastic leukemia and myelodysplastic syndromes: the use of 7AAD with antibodies to CD45 or CD34. Cytometry. 1999, 37 (4): 308-313. 10.1002\/(SICI)1097-0320(19991201)37:4<308::AID-CYTO8>3.0.CO;2-Z.","journal-title":"Cytometry"},{"issue":"2","key":"3331_CR22","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0022-1759(95)00050-K","volume":"182","author":"K Toba","year":"1995","unstructured":"Toba K, Winton EF, Koike T, Shibata A: Simultaneous three-color analysis of the surface phenotype and DNA-RNA quantitation using 7-amino-actinomycin D and pyronin Y. J Immunol Methods. 1995, 182 (2): 193-207. 10.1016\/0022-1759(95)00050-K.","journal-title":"J Immunol Methods"},{"key":"3331_CR23","unstructured":"Pallis M, Das-Gupta E: Edited by: Blumenthal RD. 2005, Totowa: Humana Press, Flow cytometric measurement of functional and phenotypic p-glycoprotein, In, Chemosensitivity, Volume 2."},{"key":"3331_CR24","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1182\/blood.V87.11.4809.bloodjournal87114809","volume":"87","author":"HJ Broxterman","year":"1996","unstructured":"Broxterman HJ, Sonneveld P, Feller N, Ossenkoppele G, Wahrer DCR, Eekman CA, Schoester M, Lankelma J, Pinedo HM, Lowenberg B, et al: Quality control of multidrug resistance assays in adult acute leukaemia: correlation between assays for P-glycoprotein expression and activity. Blood. 1996, 87: 4809-4816.","journal-title":"Blood"},{"issue":"23","key":"3331_CR25","doi-asserted-by":"publisher","first-page":"7291","DOI":"10.1158\/1078-0432.CCR-09-1222","volume":"15","author":"C Seedhouse","year":"2009","unstructured":"Seedhouse C, Grundy M, Shang S, Ronan J, Pimblett H, Russell N, Pallis M: Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine. Clin Cancer Res. 2009, 15 (23): 7291-7298. 10.1158\/1078-0432.CCR-09-1222.","journal-title":"Clin Cancer Res"},{"issue":"12","key":"3331_CR26","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1038\/sj.leu.2404439","volume":"20","author":"CH Seedhouse","year":"2006","unstructured":"Seedhouse CH, Hunter HM, Lloyd-Lewis B, Massip AM, Pallis M, Carter GI, Grundy M, Shang S, Russell NH: DNA repair contributes to the drug-resistant phenotype of primary acute myeloid leukaemia cells with FLT3 internal tandem duplications and is reversed by the FLT3 inhibitor PKC412. Leukemia. 2006, 20 (12): 2130-2136. 10.1038\/sj.leu.2404439.","journal-title":"Leukemia"},{"issue":"8","key":"3331_CR27","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1038\/sj.leu.2403846","volume":"19","author":"NI Noguera","year":"2005","unstructured":"Noguera NI, Ammatuna E, Zangrilli D, Lavorgna S, Divona M, Buccisano F, Amadori S, Mecucci C, Falini B, Lo-Coco F: Simultaneous detection of NPM1 and FLT3-ITD mutations by capillary electrophoresis in acute myeloid leukemia. Leukemia. 2005, 19 (8): 1479-1482. 10.1038\/sj.leu.2403846.","journal-title":"Leukemia"},{"issue":"3","key":"3331_CR28","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1182\/blood-2009-11-254441","volume":"116","author":"D Grimwade","year":"2010","unstructured":"Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK: Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010, 116 (3): 354-365. 10.1182\/blood-2009-11-254441.","journal-title":"Blood"},{"issue":"10","key":"3331_CR29","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1182\/blood.V86.10.3745.bloodjournal86103745","volume":"86","author":"Q-L Hao","year":"1995","unstructured":"Hao Q-L, Shah AJ, Thiemann FT, Smogorzewska EM, Crooks GM: A functional comparison of CD34+CD38- cells in cord blood and bone marrow. Blood. 1995, 86 (10): 3745-3753.","journal-title":"Blood"},{"issue":"10","key":"3331_CR30","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1002\/ijc.25806","volume":"128","author":"T Ikezoe","year":"2011","unstructured":"Ikezoe T, Yang J, Nishioka C, Kojima S, Takeuchi A, Phillip Koeffler H, Yokoyama A: Inhibition of signal transducer and activator of transcription 5 by the inhibitor of janus kinases stimulates dormant human leukemia CD34(+) \/CD38(\u2212) cells and sensitizes them to antileukemia agents. Int J Cancer. 2011, 128 (10): 2317-2325. 10.1002\/ijc.25806.","journal-title":"Int J Cancer"},{"issue":"45","key":"3331_CR31","doi-asserted-by":"publisher","first-page":"42462","DOI":"10.1074\/jbc.C100466200","volume":"276","author":"S Burma","year":"2001","unstructured":"Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ: ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem. 2001, 276 (45): 42462-42467. 10.1074\/jbc.C100466200.","journal-title":"J Biol Chem"},{"issue":"16","key":"3331_CR32","doi-asserted-by":"publisher","first-page":"5706","DOI":"10.1128\/MCB.23.16.5706-5715.2003","volume":"23","author":"K Rothkamm","year":"2003","unstructured":"Rothkamm K, Kruger I, Thompson LH, Lobrich M: Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol. 2003, 23 (16): 5706-5715. 10.1128\/MCB.23.16.5706-5715.2003.","journal-title":"Mol Cell Biol"},{"key":"3331_CR33","doi-asserted-by":"publisher","first-page":"3142","DOI":"10.1182\/blood-2002-10-3062","volume":"101","author":"Y Guan","year":"2003","unstructured":"Guan Y, Gerhard B, Hogge DE: Detection, Isolation and stimulation of quiescent primitive leukemic progenitor cells from patients with acute myeloid leukemia (AML). Blood. 2003, 101: 3142-3149. 10.1182\/blood-2002-10-3062.","journal-title":"Blood"},{"issue":"4","key":"3331_CR34","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1182\/blood-2003-02-0396","volume":"102","author":"RB Walter","year":"2003","unstructured":"Walter RB, Raden BW, Hong TC, Flowers DA, Bernstein ID, Linenberger ML: Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood. 2003, 102 (4): 1466-1473. 10.1182\/blood-2003-02-0396.","journal-title":"Blood"},{"issue":"20","key":"3331_CR35","first-page":"7525","volume":"61","author":"E Wang","year":"2001","unstructured":"Wang E, Casciano CN, Clement RP, Johnson WW: The farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product P-glycoprotein. Cancer Res. 2001, 61 (20): 7525-7529.","journal-title":"Cancer Res"},{"issue":"20","key":"3331_CR36","doi-asserted-by":"publisher","first-page":"4841","DOI":"10.1182\/blood-2008-08-172726","volume":"113","author":"JE Karp","year":"2009","unstructured":"Karp JE, Flatten K, Feldman EJ, Greer JM, Loegering DA, Ricklis RM, Morris LE, Ritchie E, Smith BD, Ironside V, et al: Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide. Blood. 2009, 113 (20): 4841-4852. 10.1182\/blood-2008-08-172726.","journal-title":"Blood"},{"issue":"2","key":"3331_CR37","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.stem.2010.05.016","volume":"7","author":"M Milyavsky","year":"2010","unstructured":"Milyavsky M, Gan OI, Trottier M, Komosa M, Tabach O, Notta F, Lechman E, Hermans KG, Eppert K, Konovalova Z, et al: A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal. Cell Stem Cell. 2010, 7 (2): 186-197. 10.1016\/j.stem.2010.05.016.","journal-title":"Cell Stem Cell"},{"issue":"21","key":"3331_CR38","first-page":"1289","volume":"118","author":"OI Gan","year":"2011","unstructured":"Gan OI, Milyavsky M, van Delft MF, Buzina A, Kalatskaya I, Ketela T, Stein L, Moffat J, Dick JE: Genome-wide shRNA screen for DNA damage response regulators in human hematopoietic stem and progenitor cells. ASH Annual Meeting Abstracts. 2011, 118 (21): 1289-","journal-title":"ASH Annual Meeting Abstracts"},{"issue":"5","key":"3331_CR39","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.tips.2011.02.014","volume":"32","author":"MD Garrett","year":"2011","unstructured":"Garrett MD, Collins I: Anticancer therapy with checkpoint inhibitors: what, where and when?. Trends Pharmacol Sci. 2011, 32 (5): 308-316. 10.1016\/j.tips.2011.02.014.","journal-title":"Trends Pharmacol Sci"},{"issue":"13","key":"3331_CR40","first-page":"4990","volume":"61","author":"C Lukas","year":"2001","unstructured":"Lukas C, Bartkova J, Latella L, Falck J, Mailand N, Schroeder T, Sehested M, Lukas J, Bartek J: DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology. Cancer Res. 2001, 61 (13): 4990-4993.","journal-title":"Cancer Res"},{"issue":"1","key":"3331_CR41","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1111\/j.1365-2362.2007.01746.x","volume":"37","author":"AW Hauswirth","year":"2007","unstructured":"Hauswirth AW, Florian S, Printz D, Sotlar K, Krauth MT, Fritsch G, Schernthaner GH, Wacheck V, Selzer E, Sperr WR, et al: Expression of the target receptor CD33 in CD34+\/CD38-\/CD123+ AML stem cells. Eur J Clin Invest. 2007, 37 (1): 73-82. 10.1111\/j.1365-2362.2007.01746.x.","journal-title":"Eur J Clin Invest"},{"issue":"17","key":"3331_CR42","doi-asserted-by":"publisher","first-page":"17ra19","DOI":"10.1126\/scitranslmed.3000349","volume":"2","author":"Y Saito","year":"2010","unstructured":"Saito Y, Kitamura H, Hijikata A, Tomizawa-Murasawa M, Tanaka S, Takagi S, Uchida N, Suzuki N, Sone A, Najima Y, et al: Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Sci Transl Med. 2010, 2 (17): 17ra19-","journal-title":"Sci Transl Med"},{"issue":"11","key":"3331_CR43","doi-asserted-by":"publisher","first-page":"4589","DOI":"10.1182\/blood-2002-07-2311","volume":"101","author":"D Amico","year":"2003","unstructured":"Amico D, Barbui AM, Erba E, Rambaldi A, Introna M, Golay J: Differential response of human acute myeloid leukemia cells to gemtuzumab ozogamicin in vitro: role of Chk1 and Chk2 phosphorylation and caspase 3. Blood. 2003, 101 (11): 4589-4597. 10.1182\/blood-2002-07-2311.","journal-title":"Blood"},{"issue":"5","key":"3331_CR44","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1182\/blood-2007-09-112730","volume":"111","author":"M Raponi","year":"2008","unstructured":"Raponi M, Lancet JE, Fan H, Dossey L, Lee G, Gojo I, Feldman EJ, Gotlib J, Morris LE, Greenberg PL, et al: A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia. Blood. 2008, 111 (5): 2589-2596. 10.1182\/blood-2007-09-112730.","journal-title":"Blood"},{"issue":"9","key":"3331_CR45","doi-asserted-by":"publisher","first-page":"3671","DOI":"10.1158\/0008-5472.CAN-04-2744","volume":"65","author":"J Pan","year":"2005","unstructured":"Pan J, She M, Xu ZX, Sun L, Yeung SC: Farnesyltransferase inhibitors induce DNA damage via reactive oxygen species in human cancer cells. Cancer Res. 2005, 65 (9): 3671-3681. 10.1158\/0008-5472.CAN-04-2744.","journal-title":"Cancer Res"},{"issue":"14","key":"3331_CR46","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1021\/bi00065a013","volume":"32","author":"PC Dedon","year":"1993","unstructured":"Dedon PC, Salzberg AA, Xu J: Exclusive production of bistranded DNA damage by calicheamicin. Biochemistry. 1993, 32 (14): 3617-3622. 10.1021\/bi00065a013.","journal-title":"Biochemistry"},{"key":"3331_CR47","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/1471-2407-4-56","volume":"4","author":"M Raponi","year":"2004","unstructured":"Raponi M, Belly RT, Karp JE, Lancet JE, Atkins D, Wang Y: Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia. BMC Cancer. 2004, 4: 56-10.1186\/1471-2407-4-56.","journal-title":"BMC Cancer"},{"issue":"10","key":"3331_CR48","doi-asserted-by":"publisher","first-page":"4168","DOI":"10.1182\/blood-2006-09-047399","volume":"109","author":"RB Walter","year":"2007","unstructured":"Walter RB, Gooley TA, van der Velden VH, Loken MR, van Dongen JJ, Flowers DA, Bernstein ID, Appelbaum FR: CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy. Blood. 2007, 109 (10): 4168-4170. 10.1182\/blood-2006-09-047399.","journal-title":"Blood"},{"issue":"4","key":"3331_CR49","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1111\/j.1365-2141.2006.06326.x","volume":"135","author":"KL Morris","year":"2006","unstructured":"Morris KL, Adams JA, Liu JA: Effect of gemtuzumab ozogamicin on acute myeloid leukemia blast cells in vitro, as a single agent and combined with other cytotoxic cells. Br J Haematol. 2006, 135 (4): 509-512. 10.1111\/j.1365-2141.2006.06326.x.","journal-title":"Br J Haematol"},{"issue":"2","key":"3331_CR50","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/sj.leu.2403205","volume":"18","author":"I Jedema","year":"2004","unstructured":"Jedema I, Barge RM, van der Velden VH, Nijmeijer BA, van Dongen JJ, Willemze R, Falkenburg JH: Internalization and cell cycle-dependent killing of leukemic cells by gemtuzumab ozogamicin: rationale for efficacy in CD33-negative malignancies with endocytic capacity. Leukemia. 2004, 18 (2): 316-325. 10.1038\/sj.leu.2403205.","journal-title":"Leukemia"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-12-431.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2407-12-431\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-12-431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-12-431.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T21:00:30Z","timestamp":1630616430000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/1471-2407-12-431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,26]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["3331"],"URL":"https:\/\/doi.org\/10.1186\/1471-2407-12-431","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,26]]},"assertion":[{"value":"24 April 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"431"}}