UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Prognosis of acute myeloid leukemia

Author
Charles A Schiffer, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

The term acute myeloid leukemia (AML) refers to a group of hematopoietic neoplasms involving cells committed to the myeloid line of cellular development. AML is characterized by a clonal proliferation of myeloid precursors with reduced capacity to differentiate into more mature cellular elements.

The response to treatment and overall survival of patients with AML is heterogeneous. A number of prognostic factors related to patient and tumor characteristics have been described for AML, including age, performance status, and karyotype (table 1) [1-3].

This topic will review prognostic factors in AML. Adverse risk factors that are more common in older adults (eg, patients over age 60 years) with AML are discussed separately. (See "Pretreatment evaluation and prognosis of acute myeloid leukemia in older adults", section on 'Outcomes in older compared with younger patients'.)

The diagnosis, treatment, complications of AML, and further information on specific cytogenetic abnormalities are also discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia" and "Cytogenetics in acute myeloid leukemia" and "Induction therapy for acute myeloid leukemia in younger adults" and "Treatment of acute myeloid leukemia in older adults" and "Overview of the complications of acute myeloid leukemia".)

CLINICAL RISK FACTORS

There are several clinical findings that may help predict the likelihood of attaining a complete remission and subsequent disease-free survival in patients with AML. The strongest adverse clinical predictors are:

                             

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Aug 16 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Sekeres MA, Peterson B, Dodge RK, et al. Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia. Blood 2004; 103:4036.
  2. Olesen LH, Aggerholm A, Andersen BL, et al. Molecular typing of adult acute myeloid leukaemia: significance of translocations, tandem duplications, methylation, and selective gene expression profiling. Br J Haematol 2005; 131:457.
  3. Estey EH. Therapeutic options for acute myelogenous leukemia. Cancer 2001; 92:1059.
  4. Shah A, Andersson TM, Rachet B, et al. Survival and cure of acute myeloid leukaemia in England, 1971-2006: a population-based study. Br J Haematol 2013; 162:509.
  5. Creutzig U, Büchner T, Sauerland MC, et al. Significance of age in acute myeloid leukemia patients younger than 30 years: a common analysis of the pediatric trials AML-BFM 93/98 and the adult trials AMLCG 92/99 and AMLSG HD93/98A. Cancer 2008; 112:562.
  6. Haferlach T, Schoch C, Löffler H, et al. Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies. J Clin Oncol 2003; 21:256.
  7. Timilshina N, Breunis H, Brandwein JM, et al. Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML? Ann Oncol 2014; 25:883.
  8. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood 2006; 107:3481.
  9. Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009; 361:1235.
  10. Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
  11. Leith CP, Kopecky KJ, Godwin J, et al. 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 1997; 89:3323.
  12. Manoharan A, Baker RI, Kyle PW. Low-dose combination chemotherapy for acute myeloid leukemia in elderly patients: a novel approach. Am J Hematol 1997; 55:115.
  13. Wahlin A, Markevärn B, Golovleva I, Nilsson M. Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia. Br J Haematol 2001; 115:25.
  14. Letendre L, Noel P, Litzow MR, et al. Treatment of acute myelogenous leukemia in the older patient with attenuated high-dose ara-C. Am J Clin Oncol 1998; 21:142.
  15. Bello C, Yu D, Komrokji RS, et al. Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome. Cancer 2011; 117:1463.
  16. Lindsley RC, Mar BG, Mazzola E, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 2015; 125:1367.
  17. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115:453.
  18. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med 2016; 374:2209.
  19. Mrózek K, Marcucci G, Nicolet D, et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol 2012; 30:4515.
  20. Herold T, Metzeler KH, Vosberg S, et al. Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis. Blood 2014; 124:1304.
  21. Pastore F, Dufour A, Benthaus T, et al. Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid leukemia. J Clin Oncol 2014; 32:1586.
  22. Ferrant A, Doyen C, Delannoy A, et al. Karyotype in acute myeloblastic leukemia: prognostic significance in a prospective study assessing bone marrow transplantation in first remission. Bone Marrow Transplant 1995; 15:685.
  23. Keating MJ, Smith TL, Kantarjian H, et al. Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome. Leukemia 1988; 2:403.
  24. Bloomfield CD, Lawrence D, Byrd JC, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res 1998; 58:4173.
  25. Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000; 96:4075.
  26. Byrd JC, Mrózek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100:4325.
  27. Delaunay J, Vey N, Leblanc T, et al. Prognosis of inv(16)/t(16;16) acute myeloid leukemia (AML): a survey of 110 cases from the French AML Intergroup. Blood 2003; 102:462.
  28. Schlenk RF, Benner A, Krauter J, et al. Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol 2004; 22:3741.
  29. Grimwade D, Hills RK, Moorman AV, et al. 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; 116:354.
  30. Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998; 92:2322.
  31. Wheatley K, Burnett AK, Goldstone AH, et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties. Br J Haematol 1999; 107:69.
  32. Appelbaum FR, Kopecky KJ, Tallman MS, et al. The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol 2006; 135:165.
  33. Breems DA, Van Putten WL, De Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 2008; 26:4791.
  34. Kayser S, Zucknick M, Döhner K, et al. Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood 2012; 119:551.
  35. Middeke JM, Beelen D, Stadler M, et al. Outcome of high-risk acute myeloid leukemia after allogeneic hematopoietic cell transplantation: negative impact of abnl(17p) and -5/5q-. Blood 2012; 120:2521.
  36. Medeiros BC, Othus M, Fang M, et al. Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. Blood 2010; 116:2224.
  37. Fang M, Storer B, Estey E, et al. Outcome of patients with acute myeloid leukemia with monosomal karyotype who undergo hematopoietic cell transplantation. Blood 2011; 118:1490.
  38. Cornelissen JJ, Breems D, van Putten WL, et al. Comparative analysis of the value of allogeneic hematopoietic stem-cell transplantation in acute myeloid leukemia with monosomal karyotype versus other cytogenetic risk categories. J Clin Oncol 2012; 30:2140.
  39. Moorman AV, Hagemeijer A, Charrin C, et al. The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. European 11q23 Workshop participants. Leukemia 1998; 12:805.
  40. Swansbury GJ, Slater R, Bain BJ, et al. Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical study of 125 cases. European 11q23 Workshop participants. Leukemia 1998; 12:792.
  41. Krauter J, Wagner K, Schäfer I, et al. Prognostic factors in adult patients up to 60 years old with acute myeloid leukemia and translocations of chromosome band 11q23: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol 2009; 27:3000.
  42. Forrest DL, Nevill TJ, Horsman DE, et al. Bone marrow transplantation for adults with acute leukaemia and 11q23 chromosomal abnormalities. Br J Haematol 1998; 103:630.
  43. Samuels BL, Larson RA, Le Beau MM, et al. Specific chromosomal abnormalities in acute nonlymphocytic leukemia correlate with drug susceptibility in vivo. Leukemia 1988; 2:79.
  44. Baer MR, Stewart CC, Lawrence D, et al. Acute myeloid leukemia with 11q23 translocations: myelomonocytic immunophenotype by multiparameter flow cytometry. Leukemia 1998; 12:317.
  45. Byrd JC, Lawrence D, Arthur DC, et al. Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with cytarabine-based chemotherapy: results from Cancer and Leukemia Group B 8461. Clin Cancer Res 1998; 4:1235.
  46. Wolman SR, Gundacker H, Appelbaum FR, et al. Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia: a Southwest Oncology Group study. Blood 2002; 100:29.
  47. Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 2001; 98:1312.
  48. Schoch C, Haferlach T, Haase D, et al. Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients. Br J Haematol 2001; 112:118.
  49. Fröhling S, Schlenk RF, Kayser S, et al. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood 2006; 108:3280.
  50. Knipp S, Hildebrand B, Kündgen A, et al. Intensive chemotherapy is not recommended for patients aged >60 years who have myelodysplastic syndromes or acute myeloid leukemia with high-risk karyotypes. Cancer 2007; 110:345.
  51. Cancer and Leukemia Group B 8461, Farag SS, Archer KJ, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood 2006; 108:63.
  52. Santamaría CM, Chillón MC, García-Sanz R, et al. Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia. Blood 2009; 114:148.
  53. Marcucci G, Mrózek K, Bloomfield CD. Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics. Curr Opin Hematol 2005; 12:68.
  54. Bienz M, Ludwig M, Leibundgut EO, et al. Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clin Cancer Res 2005; 11:1416.
  55. Marcucci G, Baldus CD, Ruppert AS, et al. Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. J Clin Oncol 2005; 23:9234.
  56. Monzo M, Brunet S, Urbano-Ispizua A, et al. Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia. Blood 2006; 107:4871.
  57. Pasqualucci L, Liso A, Martelli MP, et al. Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: Impact on WHO classification. Blood 2006; 108:4146.
  58. Marcucci G, Maharry K, Whitman SP, et al. High expression levels of the ETS-related gene, ERG, predict adverse outcome and improve molecular risk-based classification of cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B Study. J Clin Oncol 2007; 25:3337.
  59. Langer C, Radmacher MD, Ruppert AS, et al. High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood 2008; 111:5371.
  60. Andreeff M, Ruvolo V, Gadgil S, et al. HOX expression patterns identify a common signature for favorable AML. Leukemia 2008; 22:2041.
  61. Metzeler KH, Dufour A, Benthaus T, et al. ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays. J Clin Oncol 2009; 27:5031.
  62. Marcucci G, Maharry K, Wu YZ, et al. 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 2010; 28:2348.
  63. Wagner K, Damm F, Göhring G, et al. Impact of IDH1 R132 mutations and an IDH1 single nucleotide polymorphism in cytogenetically normal acute myeloid leukemia: SNP rs11554137 is an adverse prognostic factor. J Clin Oncol 2010; 28:2356.
  64. Paschka P, Schlenk RF, Gaidzik VI, et al. IDH1 and IDH2 mutations 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 2010; 28:3636.
  65. Abbas S, Lugthart S, Kavelaars FG, et al. Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value. Blood 2010; 116:2122.
  66. Green CL, Evans CM, Hills RK, et al. The prognostic significance of IDH1 mutations in younger adult patients with acute myeloid leukemia is dependent on FLT3/ITD status. Blood 2010; 116:2779.
  67. Schnittger S, Haferlach C, Ulke M, et al. 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 2010; 116:5486.
  68. Schwind S, Marcucci G, Maharry K, et al. BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 2010; 116:5660.
  69. Eisfeld AK, Marcucci G, Maharry K, et al. miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia. Blood 2012; 120:249.
  70. Paschka P, Marcucci G, Ruppert AS, et al. Wilms' tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol 2008; 26:4595.
  71. Neubauer A, Maharry K, Mrózek K, et al. Patients with acute myeloid leukemia and RAS mutations benefit most from postremission high-dose cytarabine: a Cancer and Leukemia Group B study. J Clin Oncol 2008; 26:4603.
  72. Virappane P, Gale R, Hills R, et al. Mutation of the Wilms' tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia: the United Kingdom Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 2008; 26:5429.
  73. Heuser M, Beutel G, Krauter J, et al. High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 2006; 108:3898.
  74. Summers K, Stevens J, Kakkas I, et al. Wilms' tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML. Leukemia 2007; 21:550.
  75. Hollink IH, van den Heuvel-Eibrink MM, Zimmermann M, et al. Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia. Blood 2009; 113:5951.
  76. Langer C, Marcucci G, Holland KB, et al. Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol 2009; 27:3198.
  77. Tang JL, Hou HA, Chen CY, et al. AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood 2009; 114:5352.
  78. Schnittger S, Dicker F, Kern W, et al. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood 2011; 117:2348.
  79. Gaidzik VI, Bullinger L, Schlenk RF, et al. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol 2011; 29:1364.
  80. Metzeler KH, Maharry K, Radmacher MD, et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2011; 29:1373.
  81. Yan XJ, Xu J, Gu ZH, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011; 43:309.
  82. Thol F, Damm F, Lüdeking A, et al. Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J Clin Oncol 2011; 29:2889.
  83. Green CL, Evans CM, Zhao L, et al. The prognostic significance of IDH2 mutations in AML depends on the location of the mutation. Blood 2011; 118:409.
  84. Rockova V, Abbas S, Wouters BJ, et al. Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers. Blood 2011; 118:1069.
  85. Chou WC, Chou SC, Liu CY, et al. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood 2011; 118:3803.
  86. Shen Y, Zhu YM, Fan X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood 2011; 118:5593.
  87. Hou HA, Kuo YY, Liu CY, et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood 2012; 119:559.
  88. Marcucci G, Metzeler KH, Schwind S, et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol 2012; 30:742.
  89. Gaidzik VI, Paschka P, Späth D, et al. TET2 mutations in acute myeloid leukemia (AML): results from a comprehensive genetic and clinical analysis of the AML study group. J Clin Oncol 2012; 30:1350.
  90. Ribeiro AF, Pratcorona M, Erpelinck-Verschueren C, et al. Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia. Blood 2012; 119:5824.
  91. Mendler JH, Maharry K, Radmacher MD, et al. RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures. J Clin Oncol 2012; 30:3109.
  92. Grossmann V, Schnittger S, Kohlmann A, et al. A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood 2012; 120:2963.
  93. Gaidzik VI, Schlenk RF, Paschka P, et al. Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG). Blood 2013; 121:4769.
  94. Metzeler KH, Herold T, Rothenberg-Thurley M, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016; 128:686.
  95. Schnittger S, Schoch C, Dugas M, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 2002; 100:59.
  96. Kottaridis PD, Gale RE, Linch DC. Flt3 mutations and leukaemia. Br J Haematol 2003; 122:523.
  97. Whitman SP, Archer KJ, Feng L, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res 2001; 61:7233.
  98. Fröhling S, Schlenk RF, Breitruck J, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood 2002; 100:4372.
  99. Zwaan CM, Meshinchi S, Radich JP, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood 2003; 102:2387.
  100. Pollard JA, Alonzo TA, Gerbing RB, et al. FLT3 internal tandem duplication in CD34+/CD33- precursors predicts poor outcome in acute myeloid leukemia. Blood 2006; 108:2764.
  101. Artz A, Dong X. Defining anemia by race using epidemiologic data. Blood 2008; 111:2941; author reply 2941.
  102. Schlenk RF, Döhner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008; 358:1909.
  103. Kayser S, Schlenk RF, Londono MC, et al. Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood 2009; 114:2386.
  104. Whitman SP, Maharry K, Radmacher MD, et al. FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 2010; 116:3622.
  105. Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012; 366:1079.
  106. Schmid C, Labopin M, Socié G, et al. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation. Blood 2015; 126:2062.
  107. Kottaridis PD, Gale RE, Frew ME, et al. The presence 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 first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001; 98:1752.
  108. Meshinchi S, Alonzo TA, Stirewalt DL, et al. Clinical implications of FLT3 mutations in pediatric AML. Blood 2006; 108:3654.
  109. Schneider F, Hoster E, Unterhalt M, et al. The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype. Blood 2012; 119:4383.
  110. Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 2001; 97:2434.
  111. Bacher U, Haferlach C, Kern W, et al. Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients. Blood 2008; 111:2527.
  112. Borthakur G, Kantarjian H, Patel KP, et al. Impact of numerical variation in FMS-like tyrosine kinase receptor 3 internal tandem duplications on clinical outcome in normal karyotype acute myelogenous leukemia. Cancer 2012; 118:5819.
  113. Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99:4326.
  114. Fiedler W, Serve H, Döhner H, et al. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood 2005; 105:986.
  115. Stone RM, DeAngelo DJ, Klimek V, et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 2005; 105:54.
  116. Smith BD, Levis M, Beran M, et al. Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood 2004; 103:3669.
  117. Kolitz JE. Current therapeutic strategies for acute myeloid leukaemia. Br J Haematol 2006; 134:555.
  118. Knapper S, Burnett AK, Littlewood T, et al. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 2006; 108:3262.
  119. Ravandi F, Cortes JE, Jones D, 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.
  120. Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol 2010; 28:4339.
  121. Cortes JE, Kantarjian H, Foran JM, et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol 2013; 31:3681.
  122. Levis M, Ravandi F, Wang ES, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011; 117:3294.
  123. Gale RE, Hills R, Kottaridis PD, et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood 2005; 106:3658.
  124. Brunet S, Labopin M, Esteve J, et al. Impact of FLT3 internal tandem duplication on the outcome of related and unrelated hematopoietic transplantation for adult acute myeloid leukemia in first remission: a retrospective analysis. J Clin Oncol 2012; 30:735.
  125. Falini B, Nicoletti I, Martelli MF, Mecucci C. Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features. Blood 2007; 109:874.
  126. Hollink IH, Zwaan CM, Zimmermann M, et al. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia 2009; 23:262.
  127. Schneider F, Hoster E, Unterhalt M, et al. NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS). Blood 2009; 113:5250.
  128. Becker H, Marcucci G, Maharry K, et al. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol 2010; 28:596.
  129. Falini B, Martelli MP, Bolli N, et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood 2011; 117:1109.
  130. Haferlach C, Mecucci C, Schnittger S, et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 2009; 114:3024.
  131. Döhner K, Schlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 2005; 106:3740.
  132. Verhaak RG, Goudswaard CS, van Putten W, et al. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood 2005; 106:3747.
  133. Thiede C, Koch S, Creutzig E, et al. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 2006; 107:4011.
  134. Falini B, Martelli MP, Bolli N, et al. Immunohistochemistry predicts nucleophosmin (NPM) mutations in acute myeloid leukemia. Blood 2006; 108:1999.
  135. Nerlov C. C/EBPalpha mutations in acute myeloid leukaemias. Nat Rev Cancer 2004; 4:394.
  136. Eyholzer M, Schmid S, Wilkens L, et al. The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML. Br J Cancer 2010; 103:275.
  137. Avellino R, Havermans M, Erpelinck C, et al. An autonomous CEBPA enhancer specific for myeloid-lineage priming and neutrophilic differentiation. Blood 2016; 127:2991.
  138. Marcucci G, Maharry K, Radmacher MD, et al. Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B Study. J Clin Oncol 2008; 26:5078.
  139. Fröhling S, Schlenk RF, Stolze I, et al. CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol 2004; 22:624.
  140. Pabst T, Eyholzer M, Haefliger S, et al. Somatic CEBPA mutations are a frequent second event in families with germline CEBPA mutations and familial acute myeloid leukemia. J Clin Oncol 2008; 26:5088.
  141. Boissel N, Renneville A, Biggio V, et al. Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood 2005; 106:3618.
  142. Ho PA, Alonzo TA, Gerbing RB, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 2009; 113:6558.
  143. Taskesen E, Bullinger L, Corbacioglu A, et al. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood 2011; 117:2469.
  144. Renneville A, Boissel N, Gachard N, et al. The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication. Blood 2009; 113:5090.
  145. Bacher U, Schnittger S, Macijewski K, et al. Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity. Blood 2012; 119:4719.
  146. Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, et al. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood 2009; 113:3088.
  147. Pabst T, Eyholzer M, Fos J, Mueller BU. Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis. Br J Cancer 2009; 100:1343.
  148. Dufour A, Schneider F, Metzeler KH, et al. Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol 2010; 28:570.
  149. Green CL, Koo KK, Hills RK, et al. Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol 2010; 28:2739.
  150. Figueroa ME, Wouters BJ, Skrabanek L, et al. Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features. Blood 2009; 113:2795.
  151. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009; 462:739.
  152. Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 2011; 19:17.
  153. Pietrak B, Zhao H, Qi H, et al. A tale of two subunits: how the neomorphic R132H IDH1 mutation enhances production of αHG. Biochemistry 2011; 50:4804.
  154. Losman JA, Looper RE, Koivunen P, et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 2013; 339:1621.
  155. Chaturvedi A, Araujo Cruz MM, Jyotsana N, et al. Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML. Blood 2013; 122:2877.
  156. Janin M, Mylonas E, Saada V, et al. Serum 2-hydroxyglutarate production in IDH1- and IDH2-mutated de novo acute myeloid leukemia: a study by the Acute Leukemia French Association group. J Clin Oncol 2014; 32:297.
  157. Paschka P, Marcucci G, Ruppert AS, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 2006; 24:3904.
  158. Lück SC, Russ AC, Du J, et al. KIT mutations confer a distinct gene expression signature in core binding factor leukaemia. Br J Haematol 2010; 148:925.
  159. Heidel F, Cortes J, Rücker FG, et al. Results of a multicenter phase II trial for older patients with c-Kit-positive acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) using low-dose Ara-C and Imatinib. Cancer 2007; 109:907.
  160. Gaidzik VI, Schlenk RF, Moschny S, et al. Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group. Blood 2009; 113:4505.
  161. Renneville A, Boissel N, Zurawski V, et al. Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia: a study from the Acute Leukemia French Association. Cancer 2009; 115:3719.
  162. Cilloni D, Renneville A, Hermitte F, et al. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study. J Clin Oncol 2009; 27:5195.
  163. Damm F, Heuser M, Morgan M, et al. Single nucleotide polymorphism in the mutational hotspot of WT1 predicts a favorable outcome in patients with cytogenetically normal acute myeloid leukemia. J Clin Oncol 2010; 28:578.
  164. Hou HA, Huang TC, Lin LI, et al. WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system. Blood 2010; 115:5222.
  165. Ho PA, Zeng R, Alonzo TA, et al. Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 2010; 116:702.
  166. Becker H, Marcucci G, Maharry K, et al. Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 2010; 116:788.
  167. Abdel-Wahab O, Manshouri T, Patel J, et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res 2010; 70:447.
  168. Carbuccia N, Trouplin V, Gelsi-Boyer V, et al. Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias. Leukemia 2010; 24:469.
  169. Boultwood J, Perry J, Pellagatti A, et al. Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia 2010; 24:1062.
  170. Chou WC, Huang HH, Hou HA, et al. Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood 2010; 116:4086.
  171. Schnittger S, Eder C, Jeromin S, et al. ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome. Leukemia 2013; 27:82.
  172. Metzeler KH, Becker H, Maharry K, et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood 2011; 118:6920.
  173. Micol JB, Duployez N, Boissel N, et al. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations. Blood 2014; 124:1445.
  174. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010; 363:2424.
  175. Gale RE, Lamb K, Allen C, et al. Simpson's Paradox and the Impact of Different DNMT3A Mutations on Outcome in Younger Adults With Acute Myeloid Leukemia. J Clin Oncol 2015; 33:2072.
  176. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013; 368:2059.
  177. Lacayo NJ, Meshinchi S, Kinnunen P, et al. Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes. Blood 2004; 104:2646.
  178. Bullinger L, Döhner K, Bair E, et al. Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. N Engl J Med 2004; 350:1605.
  179. Valk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med 2004; 350:1617.
  180. Wilson CS, Davidson GS, Martin SB, et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood 2006; 108:685.
  181. Rücker FG, Bullinger L, Schwaenen C, et al. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol 2006; 24:3887.
  182. Hess CJ, Berkhof J, Denkers F, et al. Activated intrinsic apoptosis pathway is a key related prognostic parameter in acute myeloid leukemia. J Clin Oncol 2007; 25:1209.
  183. Bullinger L, Döhner K, Kranz R, et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML. Blood 2008; 111:4490.
  184. Bacher U, Kohlmann A, Haferlach T. Current status of gene expression profiling in the diagnosis and management of acute leukaemia. Br J Haematol 2009; 145:555.
  185. Powell JA, Thomas D, Barry EF, et al. Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML. Blood 2009; 114:4859.
  186. Haferlach T, Kohlmann A, Wieczorek L, et al. Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group. J Clin Oncol 2010; 28:2529.
  187. Gentles AJ, Plevritis SK, Majeti R, Alizadeh AA. Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA 2010; 304:2706.
  188. Metzeler KH, Hummel M, Bloomfield CD, et al. An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia. Blood 2008; 112:4193.
  189. Silva FP, Swagemakers SM, Erpelinck-Verschueren C, et al. Gene expression profiling of minimally differentiated acute myeloid leukemia: M0 is a distinct entity subdivided by RUNX1 mutation status. Blood 2009; 114:3001.
  190. de Jonge HJ, Valk PJ, Veeger NJ, et al. High VEGFC expression is associated with unique gene expression profiles and predicts adverse prognosis in pediatric and adult acute myeloid leukemia. Blood 2010; 116:1747.
  191. Li Z, Herold T, He C, et al. Identification of a 24-gene prognostic signature that improves the European LeukemiaNet risk classification of acute myeloid leukemia: an international collaborative study. J Clin Oncol 2013; 31:1172.
  192. Radmacher MD, Marcucci G, Ruppert AS, et al. Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study. Blood 2006; 108:1677.
  193. Bullinger L, Rücker FG, Kurz S, et al. Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia. Blood 2007; 110:1291.
  194. de Jonge HJ, de Bont ES, Valk PJ, et al. AML at older age: age-related gene expression profiles reveal a paradoxical down-regulation of p16INK4A mRNA with prognostic significance. Blood 2009; 114:2869.
  195. van Rhenen A, Feller N, Kelder A, et al. High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin Cancer Res 2005; 11:6520.
  196. Greaves M. Cancer stem cells renew their impact. Nat Med 2011; 17:1046.
  197. Haferlach T, Kohlmann A, Schnittger S, et al. Global approach to the diagnosis of leukemia using gene expression profiling. Blood 2005; 106:1189.
  198. Mrózek K, Marcucci G, Paschka P, et al. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood 2007; 109:431.
  199. Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood 2005; 106:1154.
  200. Sakhinia E, Faranghpour M, Liu Yin JA, et al. Routine expression profiling of microarray gene signatures in acute leukaemia by real-time PCR of human bone marrow. Br J Haematol 2005; 130:233.
  201. Marcucci G, Radmacher MD, Maharry K, et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008; 358:1919.
  202. Garzon R, Volinia S, Liu CG, et al. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 2008; 111:3183.
  203. Jongen-Lavrencic M, Sun SM, Dijkstra MK, et al. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood 2008; 111:5078.
  204. Mi S, Lu J, Sun M, et al. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci U S A 2007; 104:19971.
  205. Li Z, Lu J, Sun M, et al. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci U S A 2008; 105:15535.
  206. Havelange V, Garzon R, Croce CM. MicroRNAs: new players in acute myeloid leukaemia. Br J Cancer 2009; 101:743.
  207. Garzon R, Heaphy CE, Havelange V, et al. MicroRNA 29b functions in acute myeloid leukemia. Blood 2009; 114:5331.
  208. Ramsingh G, Koboldt DC, Trissal M, et al. Complete characterization of the microRNAome in a patient with acute myeloid leukemia. Blood 2010; 116:5316.
  209. Marcucci G, Mrózek K, Radmacher MD, et al. The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood 2011; 117:1121.
  210. Schwind S, Maharry K, Radmacher MD, et al. Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2010; 28:5257.
  211. Marcucci G, Maharry KS, Metzeler KH, et al. Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients. J Clin Oncol 2013; 31:2086.
  212. Laupeze B, Amiot L, Drenou B, et al. High multidrug resistance protein activity in acute myeloid leukaemias is associated with poor response to chemotherapy and reduced patient survival. Br J Haematol 2002; 116:834.
  213. Legrand O, Simonin G, Perrot JY, et al. Pgp and MRP activities using calcein-AM are prognostic factors in adult acute myeloid leukemia patients. Blood 1998; 91:4480.
  214. Karászi E, Jakab K, Homolya L, et al. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia. Br J Haematol 2001; 112:308.
  215. Schaich M, Soucek S, Thiede C, et al. MDR1 and MRP1 gene expression are independent predictors for treatment outcome in adult acute myeloid leukaemia. Br J Haematol 2005; 128:324.
  216. Schaich M, Ritter M, Illmer T, et al. Mutations in ras proto-oncogenes are associated with lower mdr1 gene expression in adult acute myeloid leukaemia. Br J Haematol 2001; 112:300.
  217. Mahadevan D, List AF. Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies. Blood 2004; 104:1940.
  218. Tsuji K, Motoji T, Sugawara I, et al. Significance of lung resistance-related protein in the clinical outcome of acute leukaemic patients with reference to P-glycoprotein. Br J Haematol 2000; 110:370.
  219. Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, van Putten WL, et al. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood 2003; 101:837.
  220. Gröschel S, Lugthart S, Schlenk RF, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol 2010; 28:2101.
  221. Campos L, Oriol P, Sabido O, Guyotat D. Simultaneous expression of P-glycoprotein and BCL-2 in acute myeloid leukemia blast cells. Leuk Lymphoma 1997; 27:119.
  222. Adida C, Recher C, Raffoux E, et al. Expression and prognostic significance of survivin in de novo acute myeloid leukaemia. Br J Haematol 2000; 111:196.
  223. Kharas MG, Lengner CJ, Al-Shahrour F, et al. Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nat Med 2010; 16:903.
  224. Kolitz JE, George SL, Marcucci G, et al. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood 2010; 116:1413.
  225. Gröschel S, Schlenk RF, Engelmann J, et al. Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol 2013; 31:95.
  226. Lugthart S, Figueroa ME, Bindels E, et al. Aberrant DNA hypermethylation signature in acute myeloid leukemia directed by EVI1. Blood 2011; 117:234.
  227. Brouwer RE, Hoefnagel J, Borger van Der Burg B, et al. Expression of co-stimulatory and adhesion molecules and chemokine or apoptosis receptors on acute myeloid leukaemia: high CD40 and CD11a expression correlates with poor prognosis. Br J Haematol 2001; 115:298.
  228. Ong YL, McMullin MF, Bailie KE, et al. High bax expression is a good prognostic indicator in acute myeloid leukaemia. Br J Haematol 2000; 111:182.
  229. Del Poeta G, Venditti A, Del Principe MI, et al. Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood 2003; 101:2125.
  230. Nakase K, Kita K, Otsuji A, et al. Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells. Br J Haematol 1992; 80:317.
  231. Terwijn M, Feller N, van Rhenen A, et al. Interleukin-2 receptor alpha-chain (CD25) expression on leukaemic blasts is predictive for outcome and level of residual disease in AML. Eur J Cancer 2009; 45:1692.
  232. Gönen M, Sun Z, Figueroa ME, et al. CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900. Blood 2012; 120:2297.