[1] Amann, J. M., Nip, J., Strom, D. K., Lutterbach, B., Harada, H., Lenny, N., Downing, J.R., Meyers, S., and Hiebert, S. W. (2001). ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain.
Mol Cell Biol 21, 6470-6483 .
10.1128/MCB.21.19.6470-6483.2001[2] Appelbaum, F. R., Gundacker, H., Head, D. R., Slovak, M. L., Willman, C. L., Godwin, J. E., Anderson, J. E., and Petersdorf, S. H. (2006). Age and acute myeloid leukemia.
Blood 107, 3481-3485 .
10.1182/blood-2005-09-3724[3] Arlin, Z., Case, D. C., Moore, J., Wiernik, P., Feldman, E., Saletan, S., Desai, P., Sia, L., and Cartwright, K. (1990). Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL).
Lederle Cooperative Group. Leukemia 4, 177-183 .
[4] Barjesteh van Waalwijk van Doorn-Khosrovani, S., Erpelinck, C., Meijer, J., van Oosterhoud, S., van Putten, W. L., Valk, P. J., Berna Beverloo, H., Tenen, D. G., Lowenberg, B., and Delwel, R. (2003). Biallelic mutations in the CEBPA gene and low CEBPA expression levels as prognostic markers in intermediate-risk AML.
Hematol J 4, 31-40 .
10.1038/sj.thj.6200216[5] Bello, C., Yu, D., Komrokji, R. S., Zhu, W., Wetzstein, G. A., List, A. F., and Lancet, J. E. (2011). Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome.
Cancer 117, 1463-1469 .
10.1002/cncr.25598[6] Bennett, C. F., and Swayze, E. E. (2010). RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform.
Annu Rev Pharmacol Toxicol 50, 259-293 .
10.1146/annurev.pharmtox.010909.105654[7] Berman, E., Heller, G., Santorsa, J., McKenzie, S., Gee, T., Kempin, S., Gulati, S., Andreeff, M., Kolitz, J., and Gabrilove, J. (1991). Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia.
Blood 77, 1666-1674 .
[8] Bienz, M., Ludwig, M., Leibundgut, E. O., Mueller, B. U., Ratschiller, D., Solenthaler, M., Fey, M. F., and Pabst, T. (2005). Risk assessment in patients with acute myeloid leukemia and a normal karyotype.
Clin Cancer Res 11, 1416-1424 .
10.1158/1078-0432.CCR-04-1552[9] Bishop, J. F., Lowenthal, R. M., Joshua, D., Matthews, J. P., Todd, D., Cobcroft, R., Whiteside, M. G., Kronenberg, H., Ma, D., and Dodds, A. (1990). Etoposide in acute nonlymphocytic leukemia.
Australian Leukemia Study Group. Blood 75, 27-32 .
[10] Bishop J. F., Matthews J. P., Young G. A., Szer J., Gillett A., Joshua D., Bradstock K., Enno A., Wolf M. M., Fox R.,
. (1996). A randomized study of high-dose cytarabine in induction in acute myeloid leukemia.
Blood 87, 1710-1717 .
[11] Blum W., Garzon R., Klisovic R. B., Schwind S., Walker A., Geyer S., Liu S., Havelange V., Becker H., Schaaf L.,
. (2010). Clinical response and miR-29b predictive signifi cance in older AML patients treated with a 10-day schedule of decitabine.
Proc Natl Acad Sci U S A 107, 7473-7478 .
10.1073/pnas.1002650107[12] Blum W., Klisovic R. B., Hackanson B., Liu Z., Liu S., Devine H., Vukosavljevic T., Huynh L., Lozanski G., Kefauver C.,
. (2007). Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia.
J Clin Oncol 25, 3884-3891 .
10.1200/JCO.2006.09.4169[13] Boissel N., Nibourel O., Renneville A., Gardin C., Reman O., Contentin N., Bordessoule D., Pautas C., de Revel T., Quesnel B.,
. (2010). Prognostic impact of isocitrate dehydrogenase enzyme isoforms 1 and 2 mutations in acute myeloid leukemia: a study by the Acute Leukemia French Association group.
J Clin Oncol 28, 3717-3723 .
10.1200/JCO.2010.28.2285[14] Brandts C. H., Sargin B., Rode M., Biermann C., Lindtner B., Schw?ble J., Buerger H., Müller-Tidow C., Choudhary C., McMahon M.,
. (2005). Co nstitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation.
Cancer Res 65, 9643-9650 .
10.1158/0008-5472.CAN-05-0422[15] Bross P. F., Beitz J., Chen G., Chen X. H., Duffy E., Kieffer L., Roy S., Sridhara R., Rahman A., Williams G.,
. (2001). A pproval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia.
Clin Cancer Res 7, 1490-1496 .
[16] Bullinger, L., Ehrich, M., D?hner, K., Schlenk, R. F., D?hner, H., Nelson, M. R., and van den Boom, D. (2010). Quantitative DNA methylation predicts survival in adult acute myeloid leukemia.
Blood 115, 636-642 .
10.1182/blood-2009-03-211003[17] Burnett, A. K., Hills, R. K., Milligan, D., Kjeldsen, L., Kell, J., Russell, N. H., Yin, J. A., Hunter, A., Goldstone, A. H., and Wheatley, K. (2011). Identification of patients with acute myeloblastic leukemia who benefi t from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial.
J Clin Oncol 29, 369-377 .
10.1200/JCO.2010.31.4310[18] Burnett, A. K., Milligan, D., Prentice, A. G., Goldstone, A. H., McMullin, M. F., Hills, R. K., and Wheatley, K. (2007). A comparison of lowdose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fi t for intensive treatment.
Cancer 109, 1114-1124 .
10.1002/cncr.22496[19] Burnett A. K., Russell N. H., Hills R. K., Kell J., Freeman S., Kjeldsen L., Hunter A. E., Yin J., Craddock C. F., Dufva I. H.,
. (2012). Addi tion of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia.
J Clin Oncol 30, 3924-3931 .
10.1200/JCO.2012.42.2964[20] Büchner T., Hiddemann W., W?rmann B., L?ffl er H., Gassmann W., Haferlach T., Fonatsch C., Haase D., Schoch C., Hossfeld D.,
. (1999). Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group.
Blood 93, 4116-4124 .
[21] Callera, F., Lopes, C. O., Rosa, E. S., and Mulin, C. C. (2008). Lack of antileukemic activity of rapamycin in elderly patients with acute myeloid leukemia evolving from a myelodysplastic syndrome.
Leuk Res 32, 1633-1634 .
10.1016/j.leukres.2008.02.004[22] Cashen, A. F., Schiller, G. J., O‘Donnell, M. R., and DiPersio, J. F. (2010). Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia.
J Clin Oncol 28, 556-561 .
10.1200/JCO.2009.23.9178[23] Castaigne S., Pautas C., Terré C., Raffoux E., Bordessoule D., Bastie J.N., Legrand O., Thomas X., Turlure P., Reman O.,
. (2012). 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 379, 1508-1516 .
10.1016/S0140-6736(12)60485-1[24] Chao Q., Sprankle K. G., Grotzfeld R. M., Lai A. G., Carter T. A., Velasco A. M., Gunawardane R. N., Cramer M. D., Gardner M. F., James J.,
. (2009). Identifi c ation of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl} urea dihydrochloride (AC220), a uniquely potent, selective, and effi cacious FMS-like tyrosine kinase-3 (FLT3) inhibitor.
J Med Chem 52, 7808-7816 .
10.1021/jm9007533[25] Cortes, J., Perl, A., Smith, C., Kovacsovics, T., Dombret, H., Dohner, H., Steffen, B., Pigneux, A., Rousselot, P., Krauter, J.,
. (2011). A phase I I open-label, AC220 monotherapy effi cacy (ACE) study in patients with acute myeloid leukemia (AML) with FLT3-ITD activating mutations: Updated interim results.
Blood 118, Abstract 2576.
[26] Dillman, R. O., Davis, R. B., Green, M. R., Weiss, R. B., Gottlieb, A. J., Caplan, S., Kopel, S., Preisler, H., McIntyre, O. R., and Schiffer, C. (1991). A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B.
Blood 78, 2520-2526 .
[27] Estey, E. H. (2001). Therapeut ic options for acute myelogenous leukemia.
Cancer 92, 1059-1073 .
10.1002/1097-0142(20010901)92:5<1059::AID-CNCR1421>3.0.CO;2-K[28] Estey, E. H., Thall, P. F., Cortes, J. E., Giles, F. J., O’Brien, S., Pierce, S. A., Wang, X., Kantarjian, H. M., and Beran, M. (2001). Comparison of idarubicin+ ara-C-, fl udarabine+ ara-C-, and topotecan+ ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts.
Blood 98, 3575-3583 .
10.1182/blood.V98.13.3575[29] Fathi A. T., Arowojolu O., Swinnen I., Sato T., Rajkhowa T., Small D., Marmsater F., Robinson J. E., Gross S.D., Martinson M.,
. (2012). A potenti al therapeutic target for FLT3-ITD AML: PIM1 kinase.
Leuk Res 36, 224-231 .
10.1016/j.leukres.2011.07.011[30] Fenaux P., Mufti G. J., Hellstrom-Lindberg E., Santini V., Finelli C., Giagounidis A., Schoch R., Gattermann N., Sanz G., List A.,
. (2009). Effi cacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.
Lancet Oncol 10, 223-232 .
10.1016/S1470-2045(09)70003-8[31] Fiedler W., Mesters R., Tinnefeld H., Loges S., Staib P., Duhrsen U., Flasshove M., Ottmann O. G., Jung W., Cavalli F.,
. (2003). A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia.
Blood 102, 2763-2767 .
10.1182/blood-2002-10-2998[32] Figueroa M. E., Abdel-Wahab O., Lu C., Ward P. S., Patel J., Shih A., Li Y., Bhagwat N., Vasanthakumar A., Fernandez H. F.,
. (2010b). Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.
Cancer Cell 18, 553-567 .
10.1016/j.ccr.2010.11.015[33] Figueroa M. E., Lugthart 1, Li Y., Erpelinck-Verschueren C., Deng X., Christos P.J., Schifano E., Booth J., van Putten W., Skrabanek L.,
. (2010a). DNA methy lation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell17, 13-27 .
10.1016/j.ccr.2009.11.020[34] Gale, R. E., Green, C., Allen, C., Mead, A. J., Burnett, A. K., Hills, R. K., Linch, D. C., and Medical Research Council Adult Leukaemia Working Party. (2008). The impac t of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia.
Blood 111, 2776-2784 .
10.1182/blood-2007-08-109090[35] Gelmetti, V., Zhang, J., Fanelli, M., Minucci, S., Pelicci, P. G., and Lazar, M. A. (1998). Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO.
Mol Cell Biol 18, 7185-7191 .
[36] Grandage, V. L., Gale, R. E., Linch, D. C., and Khwaja, A. (2005). PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NFkappaB, Mapkinase and p53 pathways.
Leukemia 19, 586-594 .
[37] Green, C. L., Evans, C. M., Hills, R. K., Burnett, A. K., Linch, D. C., and Gale, R. E. (2010). The prognostic signifi cance of IDH1 mutations in younger adult patients with acute myeloid leukemia is dependent on FLT3/ITD status.
Blood 116, 2779-2782 .
10.1182/blood-2010-02-270926[38] Green, C. L., Evans, C. M., Zhao, L., Hills, R. K., Burnett, A. K., Linch, D. C., and Gale, R. E. (2011). The prognostic signifi cance of IDH2 mutations in AML depends on the location of the mutation.
Blood 118, 409-412 .
10.1182/blood-2010-12-322479[39] Grimwade, D., Hills, R. K., Moorman, A. V., Walker, H., Chatters, S., Goldstone, A. H., Wheatley, K., Harrison, C. J., Burnett, A. K., and National Cancer Research Institute Adult Leukaemia Working Group. (2010). Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic signifi cance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials.
Blood 116, 354-365 .
10.1182/blood-2009-11-254441[40] G?ttlicher M., Minucci S., Zhu P., Kr?mer O.H., Schimpf A., Giavara S., Sleeman J.P., Lo Coco F., Nervi C., Pelicci P.G.,
. (2001). Valproic ac id defi nes a novel class of HDAC inhibitors inducing differentiation of transformed cells.
EMBO J 20, 6969-6978 .
10.1093/emboj/20.24.6969[41] Haferlach, T., Kohlmann, A., Schnittger, S., Dugas, M., Hiddemann, W., Kern, W., and Schoch, C. (2005). Global approach to the diagnosis of leukemia using gene expression profi ling.
Blood 106, 1189-1198 .
10.1182/blood-2004-12-4938[42] Hann, I. M., Stevens, R. F., Goldstone, A. H., Rees, J. K., Wheatley, K., Gray, R. G., and Burnett, A. K. (1997). Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia.
Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Blood 89, 2311-2318 .
[43] Hiebert, S. W., Reed-Inderbitzin, E. F., Amann, J., Irvin, B., Durst, K., and Linggi, B. (2003). The t(8;21) fusion protein contacts corepressors and histone deacetylases to repress the transcription of the p14ARF tumor suppressor.
Blood Cells Mol Dis 30, 177-183 .
10.1016/S1079-9796(03)00021-4[44] Hinman, L. M., Hamann, P. R., Wallace, R., Menendez, A. T., Durr, F. E., and Upeslacis, J. (1993). Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics.
Cancer Res 53, 3336-3342 .
[45] Issa, J. P., Baylin, S. B., and Herman, J. G. (1997). DNA methylation changes in hematologic malignancies: biologic and clinical implications.
Leukemia 11 Suppl 1, S7-11 .
[46] Issa J. P., Garcia-Manero G., Giles F. J., Mannari R., Thomas D., Faderl S., Bayar E., Lyons J., Rosenfeld C. S., Cortes J.,
. (2004). Phase 1 stu dy of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies.
Blood 103, 1635-1640 .
10.1182/blood-2003-03-0687[47] Kantarjian H., Issa J. P., Rosenfeld C. S., Bennett J. M., Albitar M., DiPersio J., Klimek V., Slack J., de Castro C., Ravandi F.,
. (2006). Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study.
, 1794-1803 .
10.1002/cncr.21792[48] Kelly, K., Padmanabhan, S., Goy, A., Berdeja, J.G., Reeder, C.B., McDonagh, K.T., Xiaofei Zhou, X., Danaee, H., Xiao, H., Benaim, E.,
. (2011). Results fro m a Phase I multicenter trial of Alisertib (MLN8237) -an investigational aurora A kinase inhibitor-in patients with advanced hematologic malignancies.
53rd ASH Annual Meeting and Exposition . Abstract 2477 .
[49] Kim, K. T., Baird, K., Ahn, J. Y., Meltzer, P., Lilly, M., Levis, M., and Small, D. (2005). Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival.
Blood 105, 1759-1767 .
10.1182/blood-2004-05-2006[50] Kim, K. T., Levis, M., and Small, D. (2006). Constitutively activated FLT3 phosphorylates BAD partially through pim-1.
Br J Haematol 134, 500-509 .
10.1111/j.1365-2141.2006.06225.x[51] Kosugi H., Towatari M., Hatano S., Kitamura K., Kiyoi H., Kinoshita T., Tanimoto M., Murate T., Kawashima K., Saito H.,
. (1999 ). Histone dea cetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to antileukemia therapy.
Leukemia 13, 1316-1324 .
10.1038/sj.leu.2401508[52] Kottaridis P. D., Gale R. E., Frew M. E., Harrison G., Langabeer S. E., Belton A. A., Walker H., Wheatley K., Bowen D. T., Burnett A. K.,
. (2001). The presenc e of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the fi rst cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials.
Blood 98, 1752-1759 .
10.1182/blood.V98.6.1752[53] Lacasse, E. C., Kandimalla, E. R., Winocour, P., Sullivan, T., Agrawal, S., Gillard, J. W., and Durkin, J. (2005). Application of XIAP antisense to cancer and other proliferative disorders: development of AEG35156/ GEM640.
Ann N Y Acad Sci 1058, 215-234 .
10.1196/annals.1359.032[54] Leith, C. P., Kopecky, K. J., Godwin, J., McConnell, T., Slovak, M. L., Chen, I. M., Head, D. R., Appelbaum, F. R., and Willman, C. L. (1997). Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy.
A Southwest Oncology Group study. Blood 89, 3323-3329 .
[55] Leonardi, R., Subramanian, C., Jackowski, S., and Rock, C. O. (2012). Cancer-associated isocitrate dehydrogenase mutations inactivate NADPH-dependent reductive carboxylation.
J Biol Chem 287, 14615-14620 .
10.1074/jbc.C112.353946[56] Leone, G., Teofi li, L., Voso, M. T., and Lübbert, M. (2002). DNA methylation and demethylating drugs in myelodysplastic syndromes and secondary leukemias.
Haematologica 87, 1324-1341 .
[57] Letendre, L., Noel, P., Litzow, M. R., Hoagland, H. C., and Tefferi, A. (1998). Treatment of acute myelogenous leukemia in the older patient with attenuated high-dose ara-C.
Am J Clin Oncol 21, 142-144 .
10.1097/00000421-199804000-00009[58] Levis, M. and Small, D. (2003). FLT3: ITDoes matter in leukemia. Leukemia. 17-9), 1738-1752 .
10.1038/sj.leu.2403099[59] Levis, M. J., Perl, A. E., Dombret, H., D?hner, H., Steffen, B., Rousselot, P., Martinelli, P., Estey, E.H., Burnett, A. K., Gammon, G.,
. (2012). Final results of a phase 2 open-label, monotherapy effi cacy and safety study of quizartinib (AC22) in patients with FLT3-ITD positive or negative relapsed/refractory acute myeloid leukemia after second-line chemotherapy or hematopoietic stem cell transplantation.
Blood 120, Abstract 673 .
[60] Ley, T. J. (2013). Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.
N Engl J Med 368, 2059-2074 .
10.1056/NEJMoa1301689[61] Libura, J., Slater, D. J., Felix, C. A., and Richardson, C. (2005). Therapy-related acute myeloid leukemia-like MLL rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion.
Blood 105, 2124-2131 .
10.1182/blood-2004-07-2683[62] List A. F., Kopecky K. J., Willman C. L., Head D. R., Persons D. L., Slovak M. L., Dorr R., Karanes C., Hynes H. E., Doroshow J. H.,
. (2001). Benefi t of cyc losporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study.
Blood 98, 3212-3220 .
10.1182/blood.V98.12.3212[63] Lu C., Ward P. S., Kapoor G. S., Rohle D., Turcan S., Abdel-Wahab O., Edwards C. R., Khanin R., Figueroa M. E., Melnick A.,
. (2012). IDH mutation impairs histone demethylation and results in a block to cell differentiation.
Nature 483, 474-478 .
10.1038/nature10860[64] Lubbert, M., Ruter, B., Claus, R., Schmid, M., Germing, U., Eimermacher, H., Ganser, A., Platzbecker, U., Galm, O., Brugger, W.,
. (2007). Continued lo w-dose decitabine (DAC) is an active fi rstline treatment in all cytogenetic subgroups of older AML patients: Results of the FR00331 multi center phase II study.
ASH Annual Meeting Abstracts 110, 300 . L?wenberg, B. (1996). Treatment of the elderly patient with acute myeloid leukaemia.
Baillière’s clinical haematology 9, 147-159 .
[65] L?wenberg, B., Downing, J. R., and Burnett, A. (1999). Acute myeloid leukemia.
N Engl J Med 341, 1051-1062 .
10.1056/NEJM199909303411407[66] L?wenberg, B., Ossenkoppele, G. J., van Putten, W., Schouten H.C., Graux C., Ferrant A., Sonneveld P., Maertens J., Jongen-Lavrencic M., von Lilienfeld-Toal M.,
. (2009). High-dose daunorubicin in older patients with acute myeloid leukemia.
N Engl J Med 361, 1235-1248 .
10.1056/NEJMoa0901409[67] L?wenberg, B., Suciu, S., Archimbaud, E., Haak H., Stryckmans P., de Cataldo R., Dekker A.W., Berneman Z.N., Thyss A., van der Lelie J.,
. (1998). Mitox antrone versus daunorubicin in inductionconsolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: fi nal report.
European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol 16, 872-881 .
[68] L?wenberg, B., van Putten, W., Theobald, M., Gmür J., Verdonck L., Sonneveld P., Fey M., Schouten H., de Greef G., Ferrant A.,
. (2003). Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia.
N Engl J Med 349, 743-752 .
10.1056/NEJMoa025406[69] Marcucci, G., Maharry, K., Whitman, S. P., Vukosavljevic T., Paschka P., Langer C., Mrózek K., Baldus C.D., Carroll A.J., Powell B.L.,
. (2007). High exp ression levels of the ETS-related gene, ERG, predict adverse outcome and improve molecular risk-based classify cation of cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B Study.
J Clin Oncol 25, 3337-3343 .
10.1200/JCO.2007.10.8720[70] Marcucci, G., Maharry, K., Wu, Y. Z., Radmacher M. D., Mrózek K., Margeson D., Holland K. B., Whitman S. P., Becker H., Schwind S.,
. (2010). IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.
J Clin Oncol 28, 2348-2355 .
10.1200/JCO.2009.27.3730[71] Martelli, A. M., Ny?kern, M., Tabellini, G., Bortul, R., Tazzari, P. L., Evangelisti, C., and Cocco, L. (2006). Phosphoinositide 3-kinase/ Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia.
Leukemia 20, 911-928 .
10.1038/sj.leu.2404245[72] Menzin, J., Boulenger, L., Karsten, V., and Cahill, A. (2006). Effects of initial treatment on survival among elderly AML patients: Findings from the SEER-Medicare Database.
Blood 108, Abstract 1973 . Meraldi, P., Honda, R., and Nigg, E. A. (2004). Aurora kinases link chromosome segregation and cell division to cancer susceptibility.
Curr Opin Genet Dev . 14(1), 29-36 .
[73] Mohi, M. G., Boulton, C., Gu, T. L., Sternberg, D. W., Neuberg, D., Griffi n, J. D., Gilliland, D. G., and Neel, B. G. (2004). Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs.
Proc Natl Acad Sci U S A . 101(9), 3130-3135 .
10.1073/pnas.0400063101[74] Mrózek, K., Marcucci, G., Paschka, P., Whitman, S. P., and Bloomfi eld, C. D. (2007). Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classifi cation?
Blood 109, 431-448 .
10.1182/blood-2006-06-001149[75] Negrotto, S., Ng, K. P., Jankowska, A. M., Bodo, J., Gopalan, B., Guinta, K., Mulloy, J. C., His, E., Maciejewski, J., and Saunthararajah, Y. (2012). CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors.
Leukemia 26, 244-254 .
10.1038/leu.2011.207[76] Oke, A., Pearce, D., Wilkinson, R. W., Crafter, C., Odedra, R., Cavenagh, J., Fitzgibbon, J., Lister, A. T., Joel, S., and Bonnet, D. (2009). AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo.
Cancer Res 69, 4150-4158 .
10.1158/0008-5472.CAN-08-3203[77] Olesen, L. H., Aggerholm, A., Andersen, B. L., Nyvold, C. G., Guldberg, P., N?rgaard, J. M., and Hokland, P. (2005). Molecular typing of adult acute myeloid leukaemia: significance of translocations, tandem duplications, methylation, and selective gene expression profi ling.
Br J Haematol 131, 457-467 .
10.1111/j.1365-2141.2005.05791.x[78] Paschka, P., Schlenk, R. F., Gaidzik, V. I., Habdank M., Kr?nke J., Bullinger L., Sp?th D., Kayser S., Zucknick M., G?tze K.,
. (2010). IDH1 and IDH2 m utations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.
J Clin Oncol 28, 3636-3643 .
10.1200/JCO.2010.28.3762[79] Patel, J. P., Gonen, M., Figueroa, M. E., Fernandez H., Sun Z., Racevskis J., Van Vlierberghe P., Dolgalev I., Thomas S., Aminova O.,
. (2012). Prognostic rele vance of integrated genetic profi ling in acute myeloid leukemia.
N Engl J Med . 366, 1079-1089 .
10.1056/NEJMoa1112304[80] Pedersen-Bjergaard, J., Andersen, M. K., Andersen, M. T., and Christiansen, D. H. (2008). Genetics of therapy-related myelodysplasia and acute myeloid leukemia.
Leukemia 22, 240-248 .
10.1038/sj.leu.2405078[81] Pedersen-Bjergaard, J. and Philip, P. (1991). Balanced translocations involving chromosome bands 11q23 and 21q22 are highly characteristic of myelodysplasia and leukemia following therapy with cytostatic agents targeting at DNA-topoisomerase II.
Blood 78, 1147-1148 .
[82] Petersdorf, S. H., Kopecky, K. J., Slovak, M., Willman C., Nevill T., Brandwein J., Larson R. A., Erba H. P., Stiff P. J., Stuart R.K.,
. (2013). A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia.
Blood 121, 4854-4860 .
10.1182/blood-2013-01-466706[83] Pratz, K. W., Sato, T., Murphy, K. M., Stine, A., Rajkhowa, T., and Levis, M. (2010). FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML.
Blood 115, 1425-1432 .
10.1182/blood-2009-09-242859[84] Preudhomme, C., Sagot, C., Boissel, N., Cayuela J. M., Tigaud I., de Botton S., Thomas X., Raffoux E., Lamandin C., Castaigne S.,
. (2002). Favorable progn ostic signifi cance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA).
Blood 100, 2717-2723 .
10.1182/blood-2002-03-0990[85] Pui, C. H. and Relling, M. V. (2000). Topoisomerase II inhibitor-related acute myeloid leukaemia.
Br J Haematol 109, 13-23 .
10.1046/j.1365-2141.2000.01843.x[86] Rizzieri, D. A., Feldman, E., Dipersio, J. F., Gabrail, N., Stock, W., Strair, R., Rivera, V. M., Albitar, M., Bedrosian, C. L., and Giles, F. J. (2008). A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies.
Clin Cancer Res 14, 2756-2762 .
10.1158/1078-0432.CCR-07-1372[87] Rowe, J. M. and Tallman, M. S. (1997). Intensifying induction therapy in acute myeloid leukemia: has a new standard of care emerged?
Blood 90, 2121-2126 .
[88] Récher, C., Beyne-Rauzy, O., Demur, C., Chicanne, G., Dos Santos, C., Mas, V. M., Benzaquen, D., Laurent, G., Huguet, F., and Payrastre, B. (2005). Antileukemic activity of rapamycin in acute myeloid leukemia.
Blood 105, 2527-2534 .
10.1182/blood-2004-06-2494[89] Santini, V., Kantarjian, H. M., and Issa, J. P. (2001). Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications.
Ann Intern Med 134, 573-586 .
10.7326/0003-4819-134-7-200104030-00011[90] Schimmer, A. D., Estey, E. H., Borthakur, G., Carter B. Z., Schiller G. J., Tallman M. S., Altman J. K., Karp J. E., Kassis J., Hedley D. W.,
. (2009). Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia.
J Clin Oncol 27, 4741-4746 .
10.1200/JCO.2009.21.8172[91] Schnittger, S., Haferlach, C., Ulke, M., Alpermann, T., Kern, W., and Haferlach, T. (2010). IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with intermediate risk karyotype and unfavorable prognosis in adults younger than 60 years and unmutated NPM1 status.
Blood 116, 5486-5496 .
10.1182/blood-2010-02-267955[92] Sekeres, M. A., Peterson, B., Dodge, R. K., Mayer R. J., Moore J. O., Lee E. J., Kolitz J., Baer M. R., Schiffer C. A., Carroll A. J.,
. (2004). Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia.
Blood 103, 4036-4042 .
10.1182/blood-2003-09-3118[93] Shen, Y., Zhu, Y. M., Fan, X., Shi J. Y., Wang Q. R., Yan X. J., Gu Z.H., Wang Y.Y., Chen B., Jiang C. L.,
. (2011). Gene mutation pa tterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia.
Blood 118, 5593-5603 .
10.1182/blood-2011-03-343988[94] Sievers, E. L., Larson, R. A., Stadtmauer, E. A., Estey E., L?wenberg B., Dombret H., Karanes C., Theobald M., Bennett J. M., Sherman M. L.,
. (2001). Effi cacy and safe ty of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in fi rst relapse.
J Clin Oncol 19, 3244-3254 .
[95] Smith, B. D., Levis, M., Beran, M., Giles, F., Kantarjian, H., Berg, K., Murphy, K. M., Dauses, T., Allebach, J., and Small, D. (2004). Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia.
Blood 103, 3669-3676 .
10.1182/blood-2003-11-3775[96] Smith, M. A., McCaffrey, R. P., and Karp, J. E. (1996). The secondary leukemias: challenges and research directions.
J Natl Cancer Inst 88, 407-418 .
10.1093/jnci/88.7.407[97] Thiede, C., Steudel, C., Mohr, B., Schaich M., Sch?kel U., Platzbecker U., Wermke M., Bornh?user M., Ritter M., Neubauer A.,
. (2002). Analysis of FLT3-ac tivating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identifi-cation of subgroups with poor prognosis.
Blood 99, 4326-4335 .
10.1182/blood.V99.12.4326[98] Vogler, W. R., Velez-Garcia, E., Weiner, R. S., Flaum, M. A., Bartolucci, A. A., Omura, G. A., Gerber, G. A., and Banks, P. L. (1992). A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study.
J Clin Oncol 10, 1103-1111 .
[99] Wahlin, A., Markev?rn, B., Golovleva, I., and Nilsson, M. (2001). Prognostic signifi cance of risk group stratifi cation in elderly patients with acute myeloid leukaemia.
Br J Haematol 115 , 25-33 .
10.1046/j.1365-2141.2001.03043.x[100] Walsby, E., Walsh, V., Pepper, C., Burnett, A., and Mills, K. (2008). Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts.
Haematologica 93, 662-669 .
10.3324/haematol.12148[101] Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab O., Bennett B.D., Coller H.A., Cross J.R., Fantin V.R., Hedvat C.V., Perl A. E.,
. (2010). The common feature o f leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alphaketoglutarate to 2-hydroxyglutarate.
Cancer Cell 17, 225-234 .
10.1016/j.ccr.2010.01.020[102] Weick, J. K., Kopecky, K. J., Appelbaum, F. R., Head D. R., Kingsbury L. L., Balcerzak S. P., Bickers J. N., Hynes H. E., Welborn J. L., Simon S. R.,
. (1996). A randomized investi gation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study.
Blood 88, 2841-2851 .
[103] Wiernik, P. H., Banks, P. L., Case, D. C., Arlin, Z. A., Periman, P. O., Todd, M. B., Ritch, P. S., Enck, R. E., and Weitberg, A. B. (1992). Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia.
Blood 79, 313-319 .
[104] Witzig, T. E. and Kaufmann, S. H. (2006). Inhibition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in hematologic malignancies.
Curr Treat Options Oncol 7, 285-294 .
10.1007/s11864-006-0038-1[105] Yang, G., Khalaf, W., van de Locht, L., Jansen, J. H., van der Reijden, B. A., Müller-Tidow, C., Delwel, H. R., Serve, H., Clapp, D. W., and Hiebert, S. W. (2004). Epigenetic regulation of tumor suppressors in t(8:21)-containing AML.
Ann Hematol 83, 329-330 .
10.1007/s00277-003-0841-8[106] Yang, J., Ikezoe, T., Nishioka, C., Tasaka T., Taniguchi A., Kuwayama Y., Komatsu N., Bandobashi K., Togitani K., Koeffl er H. P.,
. (2007). AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo.
Blood 110, 2034-2040 .
10.1182/blood-2007-02-073700[107] Yates, J., Glidewell, O., Wiernik, P., Cooper M.R., Steinberg D., Dosik H., Levy R., Hoagland C., Henry P., Gottlieb A.,
. (1982). Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study.
Blood 60, 454-462 .
[108] Yee, K. W., Zeng, Z., Konopleva, M., Verstovsek S., Ravandi F., Ferrajoli A., Thomas D., Wierda W., Apostolidou E., Albitar M.,
. (2006). Phase I/II study of t he mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies.
Clin Cancer Res 12, 5165-5173 .
10.1158/1078-0432.CCR-06-0764[109] Zarrinkar, P. P., Gunawardane, R. N., Cramer, M. D., Gardner M. F., Brigham D., Belli B., Karaman M. W., Pratz K. W., Pallares G., Chao Q.,
. (2009). AC220 is a uniquely p otent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).
Blood 114, 2984-2992 .
10.1182/blood-2009-05-222034