O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, et al. Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15:926–57.
Döhner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015;373:1136–52.
Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, et al. The Wnt/ -Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML. Science. 2010;327:1650–3.
Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481:506–10.
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.
Shah A, Andersson TM-L, Rachet B, Björkholm M, Lambert PC. Survival and cure of acute myeloid leukaemia in England, 1971-2006: a population-based study. Br J Haematol. 2013;162:509–16.
Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127:53–61.
Ofran Y. Is the D14 bone marrow in acute myeloid leukemia still the gold standard? Curr Opin Hematol. 2016;23:108–14.
Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, et al. Phase I/II study of combination therapy with Sorafenib, Idarubicin, and Cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010;28:1856–62.
Leonard SM, Perry T, Woodman CB, Kearns P. Sequential treatment with Cytarabine and Decitabine has an increased anti-leukemia effect compared to Cytarabine alone in xenograft models of childhood acute myeloid leukemia. PLoS One. 2014;9:e87475.
Ersvaer E, Brenner AK, Vetås K, Reikvam H, Bruserud Ø. Effects of cytarabine on activation of human T cells – cytarabine has concentration-dependent effects that are modulated both by valproic acid and all-trans retinoic acid. BMC Pharmacol Toxicol. 2015;16:12.
Sekeres MA, Elson P, Kalaycio ME, Advani AS, Copelan EA, Faderl S, et al. Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood. 2009;113:28–36.
Stiehl T, Baran N, Ho AD, Marciniak-Czochra A. Clonal selection and therapy resistance in acute leukaemias: mathematical modelling explains different proliferation patterns at diagnosis and relapse. J R Soc Interface. 2014;11:20140079.
Getto P, Marciniak-Czochra A, Nakata Y, dM VM. Global dynamics of two-compartment models for cell production systems with regulatory mechanisms. Math Biosci. 2013;245:258–68.
Marciniak-Czochra A, Stiehl T, Ho AD, Jäger W, Wagner W. Modeling of asymmetric cell division in hematopoietic stem cells—regulation of self-renewal is essential for efficient repopulation. Stem Cells Dev. 2009;18:377–86.
Stiehl T, Marciniak-Czochra A. Mathematical modeling of Leukemogenesis and Cancer stem cell dynamics. Math Model Nat Phenom. 2012;7:166–202.
Cai J, Damaraju VL, Groulx N, Mowles D, Peng Y, Robins MJ, et al. Two distinct molecular mechanisms underlying Cytarabine resistance in human leukemic cells. Cancer Res. 2008;68:2349–57.
Galmarini CM, Thomas X, Calvo F, Rousselot P, Rabilloud M, El Jaffari A, et al. In vivo mechanisms of resistance to cytarabine in acute myeloid leukaemia. Br J Haematol. 2002;117:860–8.
Sawyer DB, Peng X, Chen B, Pentassuglia L, Lim CC. Mechanisms of anthracycline cardiac injury: can we identify strategies for Cardioprotection? Prog Cardiovasc Dis. 2010;53:105–13.
Minderman H, Linssen PC, Wessels JM, Haanen C. Doxorubicin toxicity in relation to the proliferative state of human hematopoietic cells. Exp Hematol. 1991;19:110–4.
Minderman H, Linssen P, van der Lely N, Wessels J, Boezeman J, de Witte T, Haanen C. Toxicity of idarubicin and doxorubicin towards normal and leukemic human bone marrow progenitors in relation to their proliferative state. Leukemia. 1994;8:382–7.
Denard B, Lee C, Ye J. Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1. elife. 2012;1:e00090.
Shinjo K, Takeshita A, Ohnishi K, Ohno R. Granulocyte Colony-stimulating factor receptor at various differentiation stages of Normal and leukemic hematopoietic cells. Leuk Lymphoma. 1997;25:37–46.
Kawada H, Sasao T, Yonekura S, Hotta T. Clinical significance of granulocyte colony-stimulating factor (G-CSF) receptor expression in acute myeloid leukemia. Leuk Res. 1998;22:31–7.
McLemore ML, Grewal S, Liu F, Archambault A, Poursine-Laurent J, Haug J, et al. STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation. Immunity. 2001;14:193–204.
Lee C, Raz R, Gimeno R, Gertner R, Wistinghausen B, Takeshita K, et al. STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation. Immunity. 2002;17:63–72.
Panopoulos AD, Watowich SS. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and ‘emergency’ hematopoiesis. Cytokine. 2008;42:277–88.
Benekli M, Xia Z, Donohue KA, Ford LA, Pixley LA, Baer MR, et al. Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival. Blood. 2002;99:252–7.
Redell MS, Ruiz MJ, Alonzo TA, Gerbing RB, Tweardy DJ. Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood. 2011;117:5701–9.
Hou H-A, Lu J-W, Lin T-Y, Tsai C-H, Chou W-C, Lin C-C, et al. Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia. Blood Cancer J. 2017;7:e588.
Jiang M, Zhang W-W, Liu P, Yu W, Liu T, Yu J. Dysregulation of SOCS-Mediated Negative Feedback of Cytokine Signaling in Carcinogenesis and Its Significance in Cancer Treatment. Front Immunol. 2017;8:70.
R Core Team (2014). R: A language and environment for statistical computing. R Found Stat Comput. Vienna: R Foundation for Statistical Computing; 2014. https://www.r-project.org.
Soetaert K, Petzoldt T, Setzer RW. Solving differential equations in R: package deSolve. J Stat Softw. 2010;33:1–25.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.
Percival M-E, Lai C, Estey E, Hourigan CS. Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia. Blood Rev. 2017;31:185–92.
Majeti R. Clonal evolution of pre-leukemic hematopoietic stem cells precedes human acute myeloid leukemia. Best Pract Res Clin Haematol. 2014;27:229–34.
Ran D, Schubert M, Taubert I, Eckstein V, Bellos F, Jauch A, et al. Heterogeneity of leukemia stem cell candidates at diagnosis of acute myeloid leukemia and their clinical significance. Exp Hematol. 2012;40:155–65.
Lichtman MA. A historical perspective on the development of the cytarabine (7days) and daunorubicin (3days) treatment regimen for acute myelogenous leukemia: 2013 the 40th anniversary of 7+3. Blood Cells Mol Dis. 2013;50:119–30.
Stone RM. The difficult problem of acute myeloid leukemia in the older adult. CA Cancer J Clin. 2002;52:363–71.
Stiehl T, Baran N, Ho AD, Marciniak-Czochra A. Cell division patterns in acute myeloid leukemia stem-like cells determine clinical course: a model to predict patient survival. Cancer Res. 2015;75:940–9.
Brons PP, Haanen C, Boezeman JB, Muus P, Holdrinet RS, Pennings AH, et al. Proliferation patterns in acute myeloid leukemia: leukemic clonogenic growth and in vivo cell cycle kinetics. Ann Hematol. 1993;66:225–33.
Del Cañizo MC, Brufau A, Almeida J, Galende J, García Marcos MA, Mota A, et al. In vitro growth in acute myeloblastic leukaemia: relationship with other clinico-biological characteristics of the disease. Br J Haematol. 1998;103:137–42.
Sun J, Ramos A, Chapman B, Johnnidis JB, Le L, Ho YJ, et al. Clonal dynamics of native haematopoiesis. Nature. 2014;514:322–7.
Klaus J, Herrmann D, Breitkreutz I, Hegenbart U, Mazitschek U, Egerer G, et al. Effect of CD34+ cell dose on hematopoietic reconstitution and outcome in 508 patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Eur J Haematol. 2007;78:21–8.
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. Blood. 1998;92:2322–33.
Köhnke T, Sauter D, Ringel K, Hoster E, Laubender RP, Hubmann M, et al. Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse. Leukemia. 2015;29:377–86.
Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012;150:264–78.
Metzeler KH, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Görlich D, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128:686–98.
McLornan DP, McMullin MF, Johnston P, Longley DB. Molecular mechanisms of drug resistance in acute myeloid leukaemia. Expert Opin Drug Metab Toxicol. 2007;3:363–77.
Hermanson DL, Das SG, Li Y, Xing C. Overexpression of Mcl-1 confers multidrug resistance, whereas topoisomerase IIβ downregulation introduces mitoxantrone-specific drug resistance in acute myeloid leukemia. Mol Pharmacol. 2013;84:236–43.
Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, et al. High-dose Daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361:1235–48.
Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361:1249–59.
Ohtake S, Miyawaki S, Fujita H, Kiyoi H, Shinagawa K, Usui N, et al. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSGAML201 study. Blood. 2011;117:2358–65.
Yin JAL, O’Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK. Minimal residual disease monitoring by RT-qPCR in core-binding factor AML allows risk-stratification and predicts relapse: results of the UK MRC AML-15 trial. Blood. 2012;120:2826–35.
Pigazzi M, Manara E, Buldini B, Beqiri V, Bisio V, Tregnago C, et al. Minimal residual disease monitored after induction therapy by rq-pcr can contribute to tailor treatment of patients with t(8;21) runx1-runx1t1 rearrangement. Haematologica. 2015;100:e99–101.
Hourigan CS, Karp JE. Minimal residual disease in acute myeloid leukaemia. Nat Rev Clin Oncol. 2013;10:460–71.
Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik V, Paschka P, Roberts N, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2202–21.
Norkin M, Chang M, An Q, Leather H, Katragadda L, Li Y, et al. A new model to predict remission status in AML patients based on day 14 bone marrow biopsy. Leuk Res. 2016;46:69–73.
Morris TA, DeCastro CM, Diehl LF, Gockerman JP, Lagoo AS, Li Z, et al. Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia. Leuk Res. 2013;37:28–31.
Ofran Y, Leiba R, Ganzel C, Saban R, Gatt M, Ram R, et al. Prospective comparison of early bone marrow evaluation on day 5 versus day 14 of the “3+7” induction regimen for acute myeloid leukemia. Am J Hematol. 2015;90:1159–64.
Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366:1079–89.
Estey EH. Acute myeloid leukemia: 2013 update on risk-stratification and management. Am J Hematol. 2013;88:318–27.
Estey E. Acute myeloid leukemia: 2016 update on risk-stratification and management. Am J Hematol. 2016;91:824–46.
Schlenk RF. Post-remission therapy for acute myeloid leukemia. Haematologica. 2014;99:1663–70.
Kohl P, Crampin EJ, Quinn TA, Noble D. Systems biology: an approach. Clin Pharmacol Ther. 2010;88:25–33.
Kitano H. Systems biology: a brief overview. Science. 2002;295:1662–4.
Antony PMA, Balling R, Vlassis N. From systems biology to systems biomedicine. Curr Opin Biotechnol. 2012;23:604–8.
Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, et al. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015;125:3878–85.
Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet. 2013;381:484–95.
Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121:4854–60.
Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, et al. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011;364:1027–36.
Campuzano-Zuluaga G, Deutsch Y, Salzberg M, Gomez A, Vargas F, Elias R, et al. Routine interim disease assessment in patients undergoing induction chemotherapy for acute myeloid leukemia: can we do better? Am J Hematol. 2016;91:277–82.
Rowe JM, Kim HT, Cassileth PA, Lazarus HM, Litzow MR, Wiernik PH, et al. Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis. Cancer. 2010;116:5012–21.
Kern W, Voskova D, Schoch C, Schnittger S, Hiddemann W, Haferlach T. Prognostic impact of early response to induction therapy as assessed by multiparameter flow cytometry in acute myeloid leukemia. Haematologica. 2004;89:528–40.
Pullarkat V, Aldoss I. Prognostic and therapeutic implications of early treatment response assessment in acute myeloid leukemia. Crit Rev Oncol Hematol. 2015;95:38–45.
Arellano M, Pakkala S, Langston A, Tighiouart M, Pan L, Chen Z, et al. Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia. Cancer. 2012;118:5278–82.