Molecular prognostic factors in cytogenetically normal acute myeloid leukemia

Expert Review of Hematology

Volumn 5, Issue 5, 2012, Pages 547-558

  Walker, Alison ^a   Marcucci, Guido ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

acute myeloid leukemia; mutational analysis; normal karyotype; prognostic markers

Indexed keywords

MICRORNA;

ACUTE GRANULOCYTIC LEUKEMIA; BIOINFORMATICS; CANCER PROGNOSIS; CLINICAL ASSESSMENT; CYTOGENETICS; GENE EXPRESSION PROFILING; GENE MUTATION; GENE TARGETING; HUMAN; KARYOTYPE; LEUKEMOGENESIS; PREDICTION; PRIORITY JOURNAL; RECURRENCE RISK; REVIEW;

DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA-BINDING PROTEINS; GENE EXPRESSION PROFILING; HUMANS; ISOCITRATE DEHYDROGENASE; LEUKEMIA, MYELOID, ACUTE; MICRORNAS; MUTATION; NEOPLASM PROTEINS; NUCLEAR PROTEINS; PROGNOSIS; RECEPTOR PROTEIN-TYROSINE KINASES;

EID: 84869192963     PISSN: 17474086     EISSN: 17474094     Source Type: Journal    
DOI: 10.1586/ehm.12.45     Document Type: Review

References (105)

1. Burnett A, Wetzler M, Löwenberg B. Therapeutic advances in acute myeloid leukemia. J. Clin. Oncol. 29(5), 487-494 (2011).
2. Byrd JC, Mrózek K, Dodge RK et al.; Cancer and Leukemia Group B (CALGB 8461). 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 100(13), 4325-4336 (2002).
3. Mrózek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev. 18(2), 115-136 (2004).
4. Döhner H, Estey EH, Amadori S et al. European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3), 453-474 (2010).
5. Swerdlow SH, Campo E, Harris NL et al. WHO classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, France (2008).
6. McKenna HJ, Stocking KL, Miller RE et al. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95(11), 3489-3497 (2000).
7. Fenski R, Flesch K, Serve S et al. Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells. Br. J. Haematol. 108(2), 322-330 (2000).
8. Mead AJ, Linch DC, Hills RK, Wheatley K, Burnett AK, Gale RE. FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood 110(4), 1262-1270 (2007).
9. Whitman SP, Ruppert AS, Radmacher MD et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood 111(3), 1552-1559 (2008).
10. Yanada M, Matsuo K, Suzuki T, Kiyoi H, Naoe T. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: A meta-analysis. Leukemia 19(8), 1345-1349 (2005).
11. Kiyoi H, Naoe T, Nakano Y et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 93(9), 3074-3080 (1999).
12. Wiernik PH. FLT3 inhibitors for the treatment of acute myeloid leukemia. Clin. Adv. Hematol. Oncol. 8(6), 429-36, 444 (2010).
13. Nakao M, Yokota S, Iwai T et al. Internal tandem duplication of the FLT3 gene found in acute myeloid leukemia. Leukemia 10(12), 1911-1918 (1996).
14. Fröhling S, Schlenk RF, Breitruck J et al.; AML Study Group Ulm. Acute myeloid leukemia. 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 100(13), 4372-4380 (2002).
15. 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 98(6), 1752-1759 (2001).
16. 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 100(1), 59-66 (2002).
17. 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 99(12), 4326-4335 (2002).
18. 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. 61(19), 7233-7239 (2001).
19. Kayser S, Schlenk RF, Londono MC et al. German-Austrian AML Study Group (AMLSG). Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood 114(12), 2386-2392 (2009).
20. Wagner K, Damm F, Thol F et al. FLT3-internal tandem duplication and age are the major prognostic factors in patients with relapsed acute myeloid leukemia with normal karyotype. Haematologica 96(5), 681-686 (2011).
21. 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 117(12), 3294-3301 (2011).
22. Schlenk RF, Döhner K, Krauter J et al.; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N. Engl. J. Med. 358(18), 1909-1918 (2008).
23. Grisendi S, Mecucci C, Falini B, Pandolfi PP. Nucleophosmin and cancer. Nat. Rev. Cancer 6(7), 493-505 (2006).
24. 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. 28(4), 596-604 (2010).
25. 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 106(12), 3740-3746 (2005).
26. Falini B, Mecucci C, Tiacci E et al.; GIMEMA Acute Leukemia Working Party. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N. Engl. J. Med. 352(3), 254-266 (2005).
27. Schlenk RF, Döhner K, Kneba M et al.; German-Austrian AML Study Group (AMLSG). Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B. Haematologica 94(1), 54-60 (2009).
28. Schlenk RF, Dohner K, Krauter J et al. All-trans retinoic acid improves outcome in younger adult patients with nucleophosmin-1 mutated acute myeloid leukemia: results of the AMLSG 07-04 randomized treatment trial. ASH Annual Meet. Abstr. 118(21), 80 (2011).
29. Schnittger S, Schoch C, Kern W et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 106(12), 3733-3739 (2005).
30. Krönke J, Schlenk RF, Jensen KO et al. Monitoring of minimal residual disease in NPM1-mutated acute myeloid leukemia: A study from the German-Austrian acute myeloid leukemia study group. J. Clin. Oncol. 29(19), 2709-2716 (2011).
31. Koschmieder S, Halmos B, Levantini E, Tenen DG. Dysregulation of the C/EBPα differentiation pathway in human cancer. J. Clin. Oncol. 27(4), 619-628 (2009).
32. Nerlov C. C/EBPα mutations in acute myeloid leukaemias. Nat. Rev. Cancer 4(5), 394-400 (2004).
33. 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. 26(31), 5078-5087 (2008).
34. Green CL, Koo KK, Hills RK, Burnett AK, Linch DC, Gale RE. 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. 28(16), 2739-2747 (2010).
35. 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. 22(4), 624-633 (2004).
36. 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 117(8), 2469-2475 (2011).
37. Ward PS, Patel J, Wise DR et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17(3), 225-234 (2010).
38. Dang L, Jin S, Su SM. IDH mutations in glioma and acute myeloid leukemia. Trends Mol. Med. 16(9), 387-397 (2010).
39. Mardis ER, Ding L, Dooling DJ et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 361(11), 1058-1066 (2009).
40. Boissel N, Nibourel O, Renneville A et al. 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(23), 3717-3723 (2010).
41. 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. 28(14), 2348-2355 (2010).
42. 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. 28(22), 3636-3643 (2010).
43. 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. 28(14), 2356-2364 (2010).
44. Patel JP, Gönen M, Figueroa ME et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N. Engl. J. Med. 366(12), 1079-1089 (2012).
45. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349(21), 2042-2054 (2003).
46. Mizuno S, Chijiwa T, Okamura T et al. Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood 97(5), 1172-1179 (2001).
47. Ley TJ, Ding L, Walter MJ et al. DNMT3A mutations in acute myeloid leukemia. N. Engl. J. Med. 363(25), 2424-2433 (2010).
48. Yamashita Y, Yuan J, Suetake I et al. Array-based genomic resequencing of human leukemia. Oncogene 29(25), 3723-3731 (2010).
49. Thol F, Damm F, Lüdeking A et al. Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J. Clin. Oncol. 29(21), 2889-2896 (2011).
50. Ribeiro AF, Pratcorona M, Erpelinck-Verschueren C et al. Mutant DNMT3A: A marker of poor prognosis in acute myeloid leukemia. Blood 119(24), 5824-5831 (2012).
51. 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. 30(7), 742-750 (2012).
52. Metzeler KH, Walker A, Geyer S et al. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia. Leukemia 26(5), 1106-1107 (2012).
53. Döhner K, Döhner H. Molecular characterization of acute myeloid leukemia. Haematologica 93(7), 976-982 (2008).
54. Tang JL, Hou HA, Chen CY et al. AML1/DNMT3A mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood 114(26), 5352-5361 (2009).
55. 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. 29(10), 1364-1372 (2011).
56. Mendler JH, Maharry K, Radmacher MD et al. Poor outcome of RUNX1-mutated (RUNX1-mut) patients (Pts) with primary, cytogenetically normal acute myeloid leukemia (CN-AML) and associated gene- and microRNA (miR) expression signatures. ASH Annual Meet. Abstr. 118(21), 3454 (2011).
57. Call KM, Glaser T, Ito CY et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 60(3), 509-520 (1990).
58. Hohenstein P, Hastie ND. The many facets of the Wilms' tumour gene, WT1. Hum. Mol. Genet. 15 Spec No 2, R196-R201 (2006).
59. Yang L, Han Y, Suarez Saiz F, Saurez Saiz F, Minden MD. A tumor suppressor and oncogene: The WT1 story. Leukemia 21(5), 868-876 (2007).
60. 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 116(5), 788-792 (2010).
61. Gaidzik VI, Schlenk RF, Moschny S et al. German-Austrian AML Study Group. Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: A study of the German-Austrian AML Study Group. Blood 113(19), 4505-4511 (2009).
62. 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. 26(28), 4595-4602 (2008).
63. 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. 26(33), 5429-5435 (2008).
64. 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. 28(4), 578-585 (2010).
65. Caligiuri MA, Schichman SA, Strout MP et al. Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocations. Cancer Res. 54(2), 370-373 (1994).
66. Ernst P, Wang J, Korsmeyer SJ. The role of MLL in hematopoiesis and leukemia. Curr. Opin. Hematol. 9(4), 282-287 (2002).
67. Caligiuri MA, Strout MP, Lawrence D et al. Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics. Cancer Res. 58(1), 55-59 (1998).
68. Döhner K, Tobis K, Ulrich R et al. Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: A study of the Acute Myeloid Leukemia Study Group Ulm. J. Clin. Oncol. 20(15), 3254-3261 (2002).
69. Whitman SP, Ruppert AS, Marcucci G et al. Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: A Cancer and Leukemia Group B study. Blood 109(12), 5164-5167 (2007).
70. Whitman SP, Liu S, Vukosavljevic T et al. The MLL partial tandem duplication: evidence for recessive gain-of-function in acute myeloid leukemia identifies a novel patient subgroup for molecular-targeted therapy. Blood 106(1), 345-352 (2005).
71. Delhommeau F, Dupont S, Della Valle V et al. Mutation in TET2 in myeloid cancers. N. Engl. J. Med. 360(22), 2289-2301 (2009).
72. Langemeijer SM, Kuiper RP, Berends M et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat. Genet. 41(7), 838-842 (2009).
73. 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. 29(10), 1373-1381 (2011).
74. 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. 30(12), 1350-1357 (2012).
75. Carbuccia N, Murati A, Trouplin V et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 23(11), 2183-2186 (2009).
76. Gelsi-Boyer V, Trouplin V, Adélaïde J et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br. J. Haematol. 145(6), 788-800 (2009).
77. Thol F, Friesen I, Damm F et al. Prognostic significance of ASXL1 mutations in patients with myelodysplastic syndromes. J. Clin. Oncol. 29(18), 2499-2506 (2011).
78. 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 118(26), 6920-6929 (2011).
79. Haferlach C, Dicker F, Herholz H, Schnittger S, Kern W, Haferlach T. Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype. Leukemia 22(8), 1539-1541 (2008).
80. 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. 26(28), 4603-4609 (2008).
81. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2), 281-297 (2004).
82. Garzon R, Garofalo M, Martelli MP et al. Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc. Natl Acad. Sci. USA 105(10), 3945-3950 (2008).
83. Garzon R, Volinia S, Liu CG et al. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 111(6), 3183-3189 (2008).
84. Li Z, Lu J, Sun M et al. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc. Natl Acad. Sci. USA 105(40), 15535-15540 (2008).
85. Marcucci G, Radmacher MD, Maharry K et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N. Engl. J. Med. 358(18), 1919-1928 (2008).
86. Mi S, Lu J, Sun M et al. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc. Natl Acad. Sci. USA 104(50), 19971-19976 (2007).
87. 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. 28(36), 5257-5264 (2010).
88. Blum W, Garzon R, Klisovic RB et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc. Natl Acad. Sci. USA 107(16), 7473-7478 (2010).
89. Oikawa T. ETS transcription factors: possible targets for cancer therapy. Cancer Sci. 95(8), 626-633 (2004).
90. Marcucci G, Maharry K, Whitman SP et al.; Cancer and Leukemia Group B Study. 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. 25(22), 3337-3343 (2007).
91. Lugthart S, van Drunen E, van Norden Y et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood 111(8), 4329-4337 (2008).
92. 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. 28(12), 2101-2107 (2010).
93. Baldus CD, Tanner SM, Ruppert AS et al. BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: A Cancer and Leukemia Group B Study. Blood 102(5), 1613-1618 (2003).
94. Langer C, Radmacher MD, Ruppert AS et al.; Cancer and Leukemia Group B (CALGB). 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 111(11), 5371-5379 (2008).
95. Sutton AL, Zhang X, Ellison TI, Macdonald PN. The 1,25(OH)2D3-regulated transcription factor MN1 stimulates vitamin D receptor-mediated transcription and inhibits osteoblastic cell proliferation. Mol. Endocrinol. 19(9), 2234-2244 (2005).
96. van Wely KH, Molijn AC, Buijs A et al. The MN1 oncoprotein synergizes with coactivators RAC3 and p300 in RAR-RXR-mediated transcription. Oncogene 22(5), 699-709 (2003).
97. 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 108(12), 3898-3905 (2006).
98. 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. 27(19), 3198-3204 (2009).
99. Damm F, Oberacker T, Thol F et al. Prognostic importance of histone methyltransferase MLL5 expression in acute myeloid leukemia. J. Clin. Oncol. 29(6), 682-689 (2011).
100. Madan V, Madan B, Brykczynska U et al. Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog MLL5. Blood 113(7), 1444-1454 (2009).
101. Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H. The protein Id: A negative regulator of helixloophelix DNA binding proteins. Cell 61(1), 49-59 (1990).
102. Tang R, Hirsch P, Fava F et al. High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia. Blood 114(14), 2993-3000 (2009).
103. 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. 27(30), 5031-5038 (2009).
104. 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 118(4), 1069-1076 (2011).
105. Estey EH. Treatment of acute myeloid leukemia. Haematologica 94(1), 10-16 (2009).