Perspective on how to approach molecular diagnostics in acute myeloid leukemia and myelodysplastic syndromes in the era of next-generation sequencing

References

• Arber DA, Brunning RD, Le Beau MM, et al. Acute myeloid leukemia with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008. pp 110–123.
   Google Scholar
• Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005;352:254–266.
   PubMed Web of Science ®Google Scholar
• 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 2005;106:3733–3739.
   PubMed Web of Science ®Google Scholar
• 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;107:4011–4020.
   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
• 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;100:59–66.
   PubMed Web of Science ®Google Scholar
• Schlenk RF, Döhner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008;358:1909–1918.
   PubMed Web of Science ®Google Scholar
• Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 2009;301:2349–2361.
   PubMed Web of Science ®Google Scholar
• Bacher U, Haferlach C, Schnittger S, et al. Interactive diagnostics in the indication to allogeneic SCT in AML. Bone Marrow Transplant 2009;43:745–756.
   PubMed Web of Science ®Google Scholar
• Lo-Coco F, Avvisati G, Orlando SM, et al. ATRA and arsenic trioxide (ATO) versus ATRA and idarubicin (AIDA) for newly diagnosed, non high-risk acute promyelocytic leukemia (APL): results of the phase III, prospective, randomized, intergroup APL0406 study by the Italian-German cooperative groups Gimema-SAL-AMLSG. Blood 2012;120(Suppl. 1): Abstract 6.
   PubMed Web of Science ®Google Scholar
• Lowenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009;361:1235–1248.
   PubMed Web of Science ®Google Scholar
• Patel JP, Gonen 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
• Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009;361:1058–1066.
   PubMed Web of Science ®Google Scholar
• Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010;363:2424–2433.
   PubMed Web of Science ®Google Scholar
• Grossmann V, Tiacci E, Holmes AB, et al. Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype. Blood 2011;118:6153–6163.
   PubMed Web of Science ®Google Scholar
• Welch JS, Ley TJ, Link DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell 2012;150:264–278.
   PubMed Web of Science ®Google Scholar
• Kon A, Shih LY, Minamino M, et al. Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat Genet 2013;45:1232–1237.
   PubMed Web of Science ®Google Scholar
• Dolnik A, Engelmann JC, Scharfenberger-Schmeer M, et al. Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing. Blood 2012;120:e83–e92.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013;368:2059–2074.
   PubMed Web of Science ®Google Scholar
• Greenberg P, Cox C, Le Beau MM, et al. International Scoring System for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079–2088.
   PubMed Web of Science ®Google Scholar
• Greenberg PL, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes. Blood 2012;120:2454–2465.
   PubMed Web of Science ®Google Scholar
• Brunning R, Orazi A, Germing U, et al. Myelodysplastic syndromes. In: Swerdlow S, Campo E, Harris NL, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008. pp 87–93.
   Google Scholar
• Papaemmanuil E, Cazzola M, Boultwood J, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011;365:1384–1395.
   PubMed Web of Science ®Google Scholar
• Yoshida K, Sanada M, Shiraishi Y, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011; 478:64–69.
   PubMed Web of Science ®Google Scholar
• Nikoloski G, Langemeijer SM, Kuiper RP, et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet 2010;42:665–667.
   PubMed Web of Science ®Google Scholar
• Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011;364:2496–2506.
   PubMed Web of Science ®Google Scholar
• 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;24:3904–3911.
   PubMed Web of Science ®Google Scholar
• Schnittger S, Kohl TM, Haferlach T, et al. KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood 2006;107:1791–1799.
   PubMed Web of Science ®Google Scholar
• Paschka P, Du J, Schlenk RF, et al. Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG). Blood 2013;121:170–177.
   PubMed Web of Science ®Google Scholar
• Slovak ML, Gundacker H, Bloomfield CD, et al. A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare “poor prognosis” myeloid malignancies. Leukemia 2006;20:1295–1297.
   PubMed Web of Science ®Google Scholar
• Chi Y, Lindgren V, Quigley S, et al. Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia: an overview. Arch Pathol Lab Med 2008;132:1835–1837.
   PubMed Web of Science ®Google Scholar
• Schnittger S, Kinkelin U, Schoch C, et al. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. Leukemia 2000;14:796–804.
   PubMed Web of Science ®Google Scholar
• 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 2002;20:3254–3261.
   PubMed Web of Science ®Google Scholar
• 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;28:570–577.
   PubMed Web of Science ®Google Scholar
• 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;117:2469–2475.
   PubMed Web of Science ®Google Scholar
• Grossmann V, Haferlach C, Nadarajah N, et al. CEBPA double-mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76.8% of cases with TET2 and GATA2 alterations impacting prognosis. Br J Haematol 2013;161:649–658.
   PubMed Web of Science ®Google Scholar
• Grossmann V, Schnittger S, Kohlmann A, et al. A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood 2012;120:2963–2972.
   PubMed Web of Science ®Google Scholar
• Thol F, Damm F, Ludeking A, et al. Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J Clin Oncol 2011;29:2889–2896.
   PubMed Web of Science ®Google Scholar
• 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;121:4769–4777.
   PubMed Web of Science ®Google Scholar
• 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 2010;28:3717–3723.
   PubMed Web of Science ®Google Scholar
• 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;27:82–91.
   PubMed Web of Science ®Google Scholar
• 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;117:2348–2357.
   PubMed Web of Science ®Google Scholar
• Visconte V, Rogers HJ, Singh J, et al. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes. Blood 2012;120:3173–3186.
   PubMed Web of Science ®Google Scholar
• Walter MJ, Ding L, Shen D, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 2011;25:1153–1158.
   PubMed Web of Science ®Google Scholar
• Thol F, Friesen I, Damm F, et al. Prognostic significance of ASXL1 mutations in patients with myelodysplastic syndromes. J Clin Oncol 2011;29:2499–2506.
   PubMed Web of Science ®Google Scholar
• Jadersten M, Saft L, Smith A, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011;29:1971–1979.
   PubMed Web of Science ®Google Scholar
• Smith AE, Mohamedali AM, Kulasekararaj A, et al. Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood 2010;116:3923–3932.
   PubMed Web of Science ®Google Scholar
• Bejar R, Stevenson KE, Caughey BA, et al. Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 2012;30:3376–3382.
   PubMed Web of Science ®Google Scholar
• Schnittger S, Bacher U, Haferlach C, et al. Diversity of the juxtamembrane and TKD1 mutations (exons 13–15) in the FLT3 gene with regards to mutant load, sequence, length, localization, and correlation with biological data. Genes Chromosomes Cancer 2012;51:910–924.
   PubMed Web of Science ®Google Scholar
• Leroy H, De Botton S, Grardel-Duflos N, et al. Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21). Leukemia 2005;19:367–372.
   PubMed Web of Science ®Google Scholar
• Grimwade D, Jovanovic JV, Hills RK, et al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol 2009;27:3650–3658.
   PubMed Web of Science ®Google Scholar
• Schnittger S, Weisser M, Schoch C, et al. New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11 + acute myeloid leukemia based on quantification of fusion transcripts. Blood 2003;102:2746–2755.
   PubMed Web of Science ®Google Scholar
• Schnittger S, Kern W, Tschulik C, et al. Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Blood 2009;114:2220–2231.
   PubMed Web of Science ®Google Scholar
• 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 2011;29:2709–2716.
   PubMed Web of Science ®Google Scholar
• Shayegi N, Kramer M, Bornhauser M, et al. The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML. Blood 2013;122:83–92.
   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
• Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 1975;94:441–448.
   PubMed Web of Science ®Google Scholar
• Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010;11:31–46.
   PubMed Web of Science ®Google Scholar
• Kohlmann A, Klein HU, Weissmann S, et al. The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories. Leukemia 2011;25:1840–1848.
   PubMed Web of Science ®Google Scholar
• Kohlmann A, Grossmann V, Nadarajah N, et al. Next-generation sequencing - feasibility and practicality in haematology. Br J Haematol 2013;160:736–753.
   PubMed Web of Science ®Google Scholar
• Kohlmann A, Nadarajah N, Alpermann T, et al. Monitoring of residual disease by next-generation deep-sequencing of RUNX1 mutations can identify acute myeloid leukemia patients with resistant disease. Leukemia 2014;28:129–137.
   PubMed Web of Science ®Google Scholar
• Margulies M, Egholm M, Altman WE, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 2005;437:376–380.
   PubMed Web of Science ®Google Scholar
• Bentley DR, Balasubramanian S, Swerdlow HP, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 2008;456:53–59.
   PubMed Web of Science ®Google Scholar
• Rothberg JM, Hinz W, Rearick TM, et al. An integrated semiconductor device enabling non-optical genome sequencing. Nature 2011;475:348–352.
   PubMed Web of Science ®Google Scholar
• Grossmann V, Roller A, Klein HU, et al. Robustness of amplicon deep sequencing underlines its utility in clinical applications. J Mol Diagn 2013;15:473–484.
   PubMed Web of Science ®Google Scholar
• Klein HU, Bartenhagen C, Kohlmann A, et al. R453Plus1Toolbox: an R/Bioconductor package for analyzing Roche 454 Sequencing data. Bioinformatics 2011;27:1162–1163.
   PubMed Web of Science ®Google Scholar
• Datta S, Datta S, Kim S, et al. Statistical analyses of next generation sequence data: a partial overview. J Proteomics Bioinform 2010;3:183–190.
   PubMedGoogle Scholar
• Nielsen R, Paul JS, Albrechtsen A, et al. Genotype and SNP calling from next-generation sequencing data. Nat Rev Genet 2011;12:443–451.
   PubMed Web of Science ®Google Scholar
• Walter MJ, Shen D, Shao J, et al. Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia 2013;27: 1275–1282.
   PubMed Web of Science ®Google Scholar
• Walter MJ, Shen D, Ding L, et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med 2012;366:1090–1098.
   PubMed Web of Science ®Google Scholar
• Ding L, Ley TJ, Larson DE, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012;481:506–510.
   PubMed Web of Science ®Google Scholar
• Kohlmann A, Grossmann V, Harbich S, et al. Monitoring of minimal residual disease using next-generation deep-sequencing in 460 acute myeloid leukemia cases identifies RUNX1 mutated patients with resistant disease. Blood 2011;118(Suppl. 1): Abstract 747.
   PubMed Web of Science ®Google Scholar
• Thol F, Kolking B, Damm F, et al. Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations. Genes Chromosomes Cancer 2012;51:689–695.
   PubMed Web of Science ®Google Scholar
• Logan AC, Gao H, Wang C, et al. High-throughput VDJ sequencing for quantification of minimal residual disease in chronic lymphocytic leukemia and immune reconstitution assessment. Proc Natl Acad Sci USA 2011;108:21194–21199.
   PubMed Web of Science ®Google Scholar
• Wu D, Sherwood A, Fromm JR, et al. High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia. Sci Transl Med 2012;4:134ra63.
   Google Scholar
• Ecker JR, Bickmore WA, Barroso I, et al. Genomics: ENCODE explained. Nature 2012;489:52–55.
   PubMedGoogle Scholar
• Green RC, Berg JS, Grody WW, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 2013;15:565–574.
   PubMed Web of Science ®Google Scholar
• Allyse M, Michie M. Not-so-incidental findings: the ACMG recommendations on the reporting of incidental findings in clinical whole genome and whole exome sequencing. Trends Biotechnol 2013;31:439–441.
   PubMed Web of Science ®Google Scholar
• Van Allen EM, Wagle N, Levy MA.Clinical analysis and interpretation of cancer genome data. J Clin Oncol 2013;31:1825–1833.
   PubMed Web of Science ®Google Scholar
• Gargis AS, Kalman L, Berry MW, et al. Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol 2012;30:1033–1036.
   PubMed Web of Science ®Google Scholar
• Godley LA. Profiles in leukemia. N Engl J Med 2012;366:1152–1153.
   PubMed Web of Science ®Google Scholar
• Voelkerding KV, Dames S, Durtschi JD. Next generation sequencing for clinical diagnostics-principles and application to targeted resequencing for hypertrophic cardiomyopathy: a paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology. J Mol Diagn 2010;12:539–551.
   PubMed Web of Science ®Google Scholar
• Zernant J, Schubert C, Im KM, et al. Analysis of the ABCA4 gene by next-generation sequencing. Invest Ophthalmol Vis Sci 2011;52: 8479–8487.
   PubMed Web of Science ®Google Scholar
• Kern W, Grossmann V, Roller A, et al. Mixed phenotype acute leukemia, T/myeloid, NOS (MPAL-TM) has a high DNMT3A mutation frequency and carries further genetic features of Both AML and T-ALL: results of a comprehensive next-generation sequencing study analyzing 32 genes. Blood 2012;120(Suppl. 1): Abstract 403.
   Google Scholar
• Owen C, Barnett M, Fitzgibbon J. Familial myelodysplasia and acute myeloid leukaemia--a review. Br J Haematol 2008;140:123–132.
   PubMed Web of Science ®Google Scholar
• Rehm HL, Bale SJ, Bayrak-Toydemir P, et al. ACMG clinical laboratory standards for next-generation sequencing. Genet Med 2013;15:733–747.
   PubMed Web of Science ®Google Scholar