A 4-gene expression prognostic signature might guide post-remission therapy in patients with intermediate-risk cytogenetic acute myeloid leukemia

References

• 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;92:2322–2333.
   PubMed Web of Science ®Google Scholar
• 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;30:4515–4523.
   PubMed Web of Science ®Google Scholar
• 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;115:453–474.
   PubMed Web of Science ®Google Scholar
• Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012;9:579–590.
   PubMed Web of Science ®Google Scholar
• 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;116:354–365.
   PubMed Web of Science ®Google Scholar
• Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366:1079–1089.
   PubMed Web of Science ®Google Scholar
• Pratcorona M, Brunet S, Nomdedéu J, et al. Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. Blood. 2013;121:2734–2738.
   PubMed Web of Science ®Google Scholar
• 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;113:3088–3091.
   PubMed Web of Science ®Google Scholar
• Valk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004;350:1617–1628.
   PubMed Web of Science ®Google Scholar
• 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;350:1605–1616.
   PubMed Web of Science ®Google Scholar
• 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;108:1677–1683.
   PubMed Web of Science ®Google Scholar
• 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;31:1172–1181.
   PubMed Web of Science ®Google Scholar
• Bullinger L, Döhner K, Kranz R, et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML. Blood. 2008;111:4490–4495.
   PubMed Web of Science ®Google Scholar
• 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;112:4193–4201.
   PubMed Web of Science ®Google Scholar
• Miller BG, Stamatoyannopoulos JA. Integrative meta-analysis of differential gene expression in acute myeloid leukemia. PLoS One. 2010;5:e9466.
   PubMed Web of Science ®Google Scholar
• Metzeler KH, Maharry K, Kohlschmidt J, et al. A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia. Leukemia. 2013;27:2023–2031.
   PubMed Web of Science ®Google Scholar
• Eppert K, Takenaka K, Lechman ER, et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med. 2011;17:1086–1093.
   PubMed Web of Science ®Google Scholar
• Hebestreit K, Gröttrup S, Emden D, et al. Leukemia gene atlas-a public platform for integrative exploration of genome-wide molecular data. PLoS One. 2012;7:e39148.
   PubMed Web of Science ®Google Scholar
• Saeed AI, Bhagabati NK, Braisted JC, et al. TM4 microarray software suite. Meth Enzymol. 2006;411:134–193.
   PubMed Web of Science ®Google Scholar
• Boissel N, Renneville A, Biggio V, et al. Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood. 2005;106:3618–3620.
   PubMed Web of Science ®Google Scholar
• 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;99:4326–4335.
   PubMed Web of Science ®Google Scholar
• 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;22:624–633.
   PubMed Web of Science ®Google Scholar
• Torsten H. On the exact distribution of maximally selected rank statistics. In: Berthold L, editor. Vol. 43. Computational statistics & data analysis. Amsterdam: Elsevier Science Publishers B. V.; 2003. p. 121–137.
   Google Scholar
• Tanner SM, Austin JL, Leone G, et al. BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia. Proc Natl Acad Sci USA. 2001;98:13901–13906.
   PubMed Web of Science ®Google Scholar
• 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;111:5371–5379.
   PubMed Web of Science ®Google Scholar
• Weber S, Alpermann T, Dicker F, et al. BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia. Blood Cancer J. 2014;4:e173.
   PubMed Web of Science ®Google Scholar
• Díaz-Beyá M, Brunet S, Nomdedéu J, et al. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia. Blood Cancer J. 2015;5:e352.
   PubMed Web of Science ®Google Scholar
• Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2016;127:29–41.
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–2221.
   PubMed Web of Science ®Google Scholar
• Bacher U, Kohlmann A, Haferlach T. Current status of gene expression profiling in the diagnosis and management of acute leukaemia. Br J Haematol. 2009;145:555–568.
   PubMed Web of Science ®Google Scholar
• Shivarov V, Bullinger L. Expression profiling of leukemia patients: key lessons and future directions. Exp Hematol. 2014;42:651–660.
   PubMed Web of Science ®Google Scholar
• Díaz-Beyá M, Brunet S, Nomdedéu J, et al. MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia. Leukemia. 2014;28:804–812.
   PubMed Web of Science ®Google Scholar
• Marcucci G, Radmacher MD, Maharry K, et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1919–1928.
   PubMed Web of Science ®Google Scholar
• Heuser M, Wingen LU, Steinemann D, et al. Gene-expression profiles and their association with drug resistance in adult acute myeloid leukemia. Haematologica. 2005;90:1484–1492.
   PubMed Web of Science ®Google Scholar
• Raponi M, Lancet JE, Fan H, et al. A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia. Blood. 2008;111:2589–2596.
   PubMed Web of Science ®Google Scholar
• 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;106:3747–3754.
   PubMed Web of Science ®Google Scholar
• Heuser M, Berg T, Kuchenbauer F, et al. Functional role of BAALC in leukemogenesis. Leukemia. 2012;26:532–536.
   PubMed Web of Science ®Google Scholar
• Haferlach C, Kern W, Schindela S, et al. Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia. Genes Chromosom Cancer. 2012;51:257–265.
   PubMed Web of Science ®Google Scholar
• Alachkar H, Santhanam R, Maharry K, et al. SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome. J Clin Invest. 2014;124:1512–1524.
   PubMed Web of Science ®Google Scholar
• Gentles AJ, Plevritis SK, Majeti R, et al. Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA. 2010;304:2706–2715.
   PubMed Web of Science ®Google Scholar
• Cheung AM, Wan TS, Leung JC, et al. Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia. 2007;21:1423–1430.
   PubMed Web of Science ®Google Scholar
• Gerber JM, Smith BD, Ngwang B, et al. A clinically relevant population of leukemic CD34(+)CD38(-) cells in acute myeloid leukemia. Blood. 2012;119:3571–3577.
   PubMed Web of Science ®Google Scholar
• Moreb JS, Ucar D, Han S, et al. The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance. Chem Biol Interact. 2012;195:52–60.
   PubMed Web of Science ®Google Scholar
• 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;31:2086–2093.
   PubMed Web of Science ®Google Scholar
• Shahbazi J, Lock R, Liu T. Tumor protein 53-induced nuclear protein 1 enhances p53 function and represses tumorigenesis. Front Genet. 2013;4:80.
   PubMedGoogle Scholar
• Zhang J, Cheng C, Yuan X, et al. microRNA-155 acts as an oncogene by targeting the tumor protein 53-induced nuclear protein 1 in esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7:602–610.
   PubMed Web of Science ®Google Scholar