Update on cytogenetic and molecular changes in myelodysplastic syndromes

References

• Swerdlow SH, Campo E, Harris NL, . WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008.
   Google Scholar
• Greenberg P, Cox C, LeBeau MM, . International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079–2088.
   PubMed Web of Science ®Google Scholar
• Malcovati L, Germing U, Kuendgen A, . Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007;25: 3503–3510.
   PubMed Web of Science ®Google Scholar
• Schanz J, Steidl C, Fonatsch C, . Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the international prognostic scoring system. J Clin Oncol 2011;29:1963–1970.
   PubMed Web of Science ®Google Scholar
• Ernst T, Chase AJ, Score J, . Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010;42:722–726.
   PubMed Web of Science ®Google Scholar
• Langemeijer SM, Kuiper RP, Berends M, . Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 2009;41:838–842.
   PubMed Web of Science ®Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, . Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009;10:223–232.
   PubMed Web of Science ®Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, . Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010;28:562–569.
   PubMed Web of Science ®Google Scholar
• Mitelman F, Johansson B, Mertens F. Mitelman database of chromosome aberrations and gene fusions in cancer. 2011. Available from: http://cgap.nci.nih.gov/Chromosomes/Mitelman
   Google Scholar
• Pedersen-Bjergaard J, Andersen MK, Christiansen DH, . Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. Blood 2002;99:1909–1912.
   PubMed Web of Science ®Google Scholar
• Lugthart S, Groschel S, Beverloo HB, . Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol 2010;28:3890–3898.
   PubMed Web of Science ®Google Scholar
• Soekarman D, von Lindern M, Daenen S, . The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. Blood 1992;79:2990–2997.
   PubMed Web of Science ®Google Scholar
• Sobulo OM, Borrow J, Tomek R, . MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). Proc Natl Acad Sci USA 1997;94:8732–8737.
   PubMed Web of Science ®Google Scholar
• Bousquet M, Quelen C, Rosati R, . Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation. J Exp Med 2008;205:2499–2506.
   PubMed Web of Science ®Google Scholar
• Pedersen-Bjergaard J, Andersen MT, Andersen MK. Genetic pathways in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2007:392–397.
   PubMedGoogle Scholar
• Patnaik MM, Lasho TL, Finke CM, . Isolated del(5q) in myeloid malignancies: clinicopathologic and molecular features in 143 consecutive patients. Am J Hematol 2011;86:393–398.
   PubMed Web of Science ®Google Scholar
• Mallo M, Cervera J, Schanz J, . Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q. Leukemia 2011;25: 110–120.
   PubMed Web of Science ®Google Scholar
• Boultwood J, Pellagatti A, McKenzie AN, Wainscoat JS. Advances in the 5q- syndrome. Blood 2010;116:5803–5811.
   PubMed Web of Science ®Google Scholar
• List A, Dewald G, Bennett J, . Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355:1456–1465.
   PubMed Web of Science ®Google Scholar
• Gohring G, Giagounidis A, Busche G, . Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression. Ann Hematol 2010;89:365–374.
   PubMed Web of Science ®Google Scholar
• Gohring G, Giagounidis A, Busche G, . Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization:implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide. Haematologica 2011;96:319–322.
   PubMed Web of Science ®Google Scholar
• Jadersten M, Saft L, Smith A, . 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
• Gohring G, Lange K, Hofmann W, . Telomere shortening, clonal evolution and disease progression in myelodysplastic syndrome patients with 5q deletion treated with lenalidomide. Leukemia 2012;26:356–358.
   PubMed Web of Science ®Google Scholar
• Tehranchi R, Woll PS, Anderson K, . Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med 2010;363:1025–1037.
   PubMed Web of Science ®Google Scholar
• Ebert BL, Pretz J, Bosco J, . Identification of RPS14 as a 5q-syndrome gene by RNA interference screen. Nature 2008;451:335–339.
   PubMed Web of Science ®Google Scholar
• Barlow JL, Drynan LF, Hewett DR, . A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. Nat Med 2010;16:59–66.
   PubMed Web of Science ®Google Scholar
• Pellagatti A, Marafioti T, Paterson JC, . Induction of p53 and up-regulation of the p53 pathway in the human 5q- syndrome. Blood 2010;115:2721–2723.
   PubMed Web of Science ®Google Scholar
• Dutt S, Narla A, Lin K, . Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 2011;117:2567–2576.
   PubMed Web of Science ®Google Scholar
• Joslin JM, Fernald AA, Tennant TR, . Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders. Blood 2007;110:719–726.
   PubMed Web of Science ®Google Scholar
• Liu TX, Becker MW, Jelinek J, . Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Nat Med 2007;13:78–83.
   PubMed Web of Science ®Google Scholar
• Starczynowski DT, Kuchenbauer F, Argiropoulos B, . Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat Med 2010;16:49–58.
   PubMed Web of Science ®Google Scholar
• La Starza R, Matteucci C, Gorello P, . NPM1 deletion is associated with gross chromosomal rearrangements in leukemia. PLoS One 2010;5:e12855.
   PubMed Web of Science ®Google Scholar
• Hasle H, Niemeyer CM. Advances in the prognostication and management of advanced MDS in children. Br J Haematol 2011;154:185–195.
   PubMed Web of Science ®Google Scholar
• Strahm B, Nollke P, Zecca M, . Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia 2011;25:455–462.
   PubMed Web of Science ®Google Scholar
• Haase D, Germing U, Schanz J, . New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 2007;110:4385–4395.
   PubMed Web of Science ®Google Scholar
• Gohring G, Karow A, Steinemann D, . Chromosomal aberrations in congenital bone marrow failure disorders—an early indicator for leukemogenesis? Ann Hematol 2007;86:733–739.
   PubMed Web of Science ®Google Scholar
• Niemeyer CM, Kratz CP. Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia: molecular classification and treatment options. Br J Haematol 2008;140:610–624.
   PubMed Web of Science ®Google Scholar
• Stein S, Ott MG, Schultze-Strasser S, . Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med 2010;16:198–204.
   PubMed Web of Science ®Google Scholar
• Praulich I, Tauscher M, Gohring G, . Clonal heterogeneity in childhood myelodysplastic syndromes—challenge for the detection of chromosomal imbalances by array-CGH. Genes Chromosomes Cancer 2010;49:885–900.
   PubMed Web of Science ®Google Scholar
• Lange K, Holm L, Vang Nielsen K, . Telomere shortening and chromosomal instability in myelodysplastic syndromes. Genes Chromosomes Cancer 2010;49:260–269.
   PubMed Web of Science ®Google Scholar
• De Weer A, Poppe B, Vergult S, . Identification of two critically deleted regions within chromosome segment 7q35-q36 in EVI1 deregulated myeloid leukemia cell lines. PLoS One 2010;5:e8676.
   PubMed Web of Science ®Google Scholar
• Asou H, Matsui H, Ozaki Y, . Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome. Biochem Biophys Res Commun 2009;383:245–251.
   PubMed Web of Science ®Google Scholar
• Curtiss NP, Bonifas JM, Lauchle JO, . Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22. Genomics 2005;85:600–607.
   PubMed Web of Science ®Google Scholar
• Wong JC, Zhang Y, Lieuw KH, . Use of chromosome engineering to model a segmental deletion of chromosome band 7q22 found in myeloid malignancies. Blood 2010;115:4524–4532.
   PubMed Web of Science ®Google Scholar
• Emerling BM, Bonifas J, Kratz CP, . MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia. Oncogene 2002;21:4849–4854.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Wong J, Klinger M, . MLL5 contributes to hematopoietic stem cell fitness and homeostasis. Blood 2009;113: 1455–1463.
   PubMed Web of Science ®Google Scholar
• Madan V, Madan B, Brykczynska U, . Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog MLL5. Blood 2009;113:1444–1454.
   PubMedGoogle Scholar
• Heuser M, Yap DB, Leung M, . Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood 2009;113:1432–1443.
   PubMed Web of Science ®Google Scholar
• Fujiki R, Chikanishi T, Hashiba W, . GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature 2009;459:455–459.
   PubMedGoogle Scholar
• Damm F, Oberacker T, Thol F, . Prognostic importance of histone methyltransferase MLL5 expression in acute myeloid leukemia. J Clin Oncol 2011;29:682–689.
   PubMed Web of Science ®Google Scholar
• Vardiman JW, Thiele J, Arber DA, . The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937–951.
   PubMed Web of Science ®Google Scholar
• Agis H, Mannhalter C, Sperr WR, . Detection of trisomy 8 in donor-derived Ph- cells in a patient with Ph + chronic myeloid leukemia successfully treated with imatinib (STI571) in relapse after allogeneic transplantation. Leuk Lymphoma 2004;45:1453–1458.
   PubMed Web of Science ®Google Scholar
• Andersen MK, Pedersen-Bjergaard J, Kjeldsen L, . Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8. Leukemia 2002;16:1390–1393.
   PubMed Web of Science ®Google Scholar
• Terre C, Eclache V, Rousselot P, . Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia. Leukemia 2004;18:1340–1346.
   PubMed Web of Science ®Google Scholar
• Maserati E, Aprili F, Vinante F, . Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases. Genes Chromosomes Cancer 2002;33:93–97.
   PubMed Web of Science ®Google Scholar
• Ripperger T, Tauscher M, Praulich I, . Constitutional trisomy 8p11.21-q11.21 mosaicism: a germline alteration predisposing to myeloid leukemia. Br J Haematol 2011;155:209–217.
   PubMed Web of Science ®Google Scholar
• Mufti G, Giagounidis A, Skikne B, . Occurrence of trisomy 8 (+8) in patients with low- or int-1-risk MDS with deletion 5q [del(5q)] treated with lenalidomide. Leuk Res 2011;35:S87: Abstract 221.
   PubMed Web of Science ®Google Scholar
• Virtaneva K, Wright FA, Tanner SM, . Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Natl Acad Sci USA 2001;98:1124–1129.
   PubMed Web of Science ®Google Scholar
• Mallo M, Luno E, Sanzo C, . Clinical impact of the clone size in MDS cases with monosomy 7 or 7q deletion, trisomy 8, 20q deletion and loss of Y chromosome. Leuk Res 2011;35:834–836.
   PubMed Web of Science ®Google Scholar
• Breems DA, Van Putten WL, De Greef GE, . Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 2008;26:4791–4797.
   PubMed Web of Science ®Google Scholar
• Raza S, TaherNazerHussain F, Patnaik M, . Autosomal monosomies among 24,262 consecutive cytogenetic studies:prevalence, chromosomal distribution and clinicopathologic correlates of sole abnormalities. Am J Hematol 2011;86:353–356.
   PubMed Web of Science ®Google Scholar
• Belli CB, Bengio R, Aranguren PN, . Partial and total monosomal karyotypes in myelodysplastic syndromes: comparative prognostic relevance among 421 patients. Am J Hematol 2011;86: 540–545.
   PubMed Web of Science ®Google Scholar
• Patnaik MM, Hanson CA, Hodnefield JM, . Monosomal karyotype in myelodysplastic syndromes, with or without monosomy 7 or 5, is prognostically worse than an otherwise complex karyotype. Leukemia 2011;25:266–270.
   PubMed Web of Science ®Google Scholar
• Gohring G, Michalova K, Beverloo HB, . Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood 2010;116:3766–3769.
   PubMed Web of Science ®Google Scholar
• Galvan AB, Mallo M, Arenillas L, . Does monosomy 5 really exist in myelodysplastic syndromes and acute myeloid leukemia? Leuk Res 2010;34:1242–1245.
   PubMed Web of Science ®Google Scholar
• Chun K, Hagemeijer A, Iqbal A, . Implementation of standardized international karyotype scoring practices is needed to provide uniform and systematic evaluation for patients with myelodysplastic syndrome using IPSS criteria: an International Working Group on MDS Cytogenetics Study. Leuk Res 2010;34:160–165.
   PubMed Web of Science ®Google Scholar
• Delhommeau F, Dupont S, Della Valle V, . Mutation in TET2 in myeloid cancers. N Engl J Med 2009;360:2289–2301.
   PubMed Web of Science ®Google Scholar
• Bejar R, Stevenson K, Abdel-Wahab O, . Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011; 364:2496–2506.
   PubMed Web of Science ®Google Scholar
• Gondek LP, Tiu R, O'Keefe CL, . Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood 2008;111:1534–1542.
   PubMed Web of Science ®Google Scholar
• Mohamedali A, Gaken J, Twine NA, . Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood 2007;110:3365–3373.
   PubMed Web of Science ®Google Scholar
• Ito S, D'Alessio AC, Taranova OV, . Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010;466:1129–1133.
   PubMed Web of Science ®Google Scholar
• Figueroa ME, Abdel-Wahab O, Lu C, . Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010;18:553–567.
   PubMed Web of Science ®Google Scholar
• Xu W, Yang H, Liu Y, . Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 2011;19:17–30.
   PubMed Web of Science ®Google Scholar
• Moran-Crusio K, Reavie L, Shih A, . Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 2011;20:11–24.
   PubMed Web of Science ®Google Scholar
• Quivoron C, Couronné L, Della Valle V, . TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 2011;20:25–38.
   PubMed Web of Science ®Google Scholar
• Jankowska AM, Szpurka H, Tiu RV, . Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 2009;113:6403–6410.
   PubMed Web of Science ®Google Scholar
• Kosmider O, Gelsi-Boyer V, Cheok M, . TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood 2009;114:3285–3291.
   PubMed Web of Science ®Google Scholar
• Smith AE, Mohamedali AM, Kulasekararaj A, . 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
• Itzykson R, Kosmider O, Cluzeau T, . Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 2011;25:1147–1152.
   PubMed Web of Science ®Google Scholar
• Rocquain J, Carbuccia N, Trouplin V, . Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. BMC Cancer 2010;10:401.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Greenberg PL, Bennett JM, . Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006;108:419–425.
   PubMed Web of Science ®Google Scholar
• Gelsi-Boyer V, Trouplin V, Adelaide J, . Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol 2009;145:788–800.
   PubMed Web of Science ®Google Scholar
• Boultwood J, Perry J, Pellagatti A, . Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia 2010;24:1062–1065.
   PubMed Web of Science ®Google Scholar
• Thol F, Friesen I, Damm F, . Prognostic significance of ASXL1 mutations in patients with myelodysplastic syndromes. J Clin Oncol 2011;29:2499–2506.
   PubMed Web of Science ®Google Scholar
• Abdel-Wahab O, Kilpivaara O, Patel J, . The most commonly reported variant in ASXL1 (c.1934dupG;p.Gly646TrpfsX12) is not a somatic alteration. Leukemia 2010;24:1656–1657.
   PubMed Web of Science ®Google Scholar
• Carbuccia N, Murati A, Trouplin V, . Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 2009;23:2183–2186.
   PubMed Web of Science ®Google Scholar
• Boultwood J, Perry J, Zaman R, . High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia 2010;24:1139–1145.
   PubMed Web of Science ®Google Scholar
• Fisher CL, Pineault N, Brookes C, . Loss-of-function Additional sex combs like 1 mutations disrupt hematopoiesis but do not cause severe myelodysplasia or leukemia. Blood 2010;115:38–46.
   PubMed Web of Science ®Google Scholar
• Fisher CL, Randazzo F, Humphries RK, . Characterization of Asxl1, a murine homolog of Additional sex combs, and analysis of the Asx-like gene family. Gene 2006;369:109–118.
   PubMed Web of Science ®Google Scholar
• Lee SW, Cho YS, Na JM, . ASXL1 represses retinoic acid receptor-mediated transcription through associating with HP1 and LSD1. J Biol Chem 2010;285:18–29.
   PubMed Web of Science ®Google Scholar
• Cho YS, Kim EJ, Park UH, . Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor. J Biol Chem 2006;281:17588–17598.
   PubMed Web of Science ®Google Scholar
• Nikoloski G, Langemeijer SM, Kuiper RP, . Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet 2010;42:665–667.
   PubMed Web of Science ®Google Scholar
• Kulasekararaj A, Mohamedali A, Smith AE, . Polycomb complex group gene mutations and their prognostic relevance in 5-azacitidine treated myelodysplastic syndrome patients. Blood 2010;116(Suppl. 1): Abstract 125.
   PubMed Web of Science ®Google Scholar
• Thol F, Heuser M, Damm F, . DNMT3A mutations are rare in childhood acute myeloid leukemia. Haematologica 2011;96:1238–1240.
   PubMed Web of Science ®Google Scholar
• Walter MJ, Ding L, Shen D, . Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 2011;25:1153–1158.
   PubMed Web of Science ®Google Scholar
• Broske AM, Vockentanz L, Kharazi S, . DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. Nat Genet 2009;41:1207–1215.
   PubMed Web of Science ®Google Scholar
• Yamashita Y, Yuan J, Suetake I, . Array-based genomic resequencing of human leukemia. Oncogene 2010;29:3723–3731.
   PubMed Web of Science ®Google Scholar
• Yan XJ, Xu J, Gu ZH, . Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011;43:309–315.
   PubMed Web of Science ®Google Scholar
• Ley TJ, Ding L, Walter MJ, . DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010;363:2424–2433.
   PubMed Web of Science ®Google Scholar
• Mardis ER, Ding L, Dooling DJ, . Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009;361:1058–1066.
   PubMed Web of Science ®Google Scholar
• Ward PS, Patel J, Wise DR, . The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010;17:225–234.
   PubMed Web of Science ®Google Scholar
• Thol F, Weissinger EM, Krauter J, . IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica 2010;95:1668–1674.
   PubMed Web of Science ®Google Scholar
• Kosmider O, Gelsi-Boyer V, Slama L, . Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms. Leukemia 2010;24:1094–1096.
   PubMed Web of Science ®Google Scholar
• Yoshida K, Sanada M, Kato M, . A nonsense mutation of IDH1 in myelodysplastic syndromes and related disorders. Leukemia 2011;25:184–186.
   Google Scholar
• Huang G, Zhang P, Hirai H, . PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet 2008;40:51–60.
   PubMed Web of Science ®Google Scholar
• Watanabe-Okochi N, Kitaura J, Ono R, . AML1 mutations induced MDS and MDS/AML in a mouse BMT model. Blood 2008;111:4297–4308.
   PubMed Web of Science ®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
• Ripperger T, Steinemann D, Gohring G, . A novel pedigree with heterozygous germline RUNX1 mutation causing familial MDS-related AML: can these families serve as a multistep model for leukemic transformation? Leukemia 2009;23:1364–1366.
   PubMed Web of Science ®Google Scholar
• Owen CJ, Toze CL, Koochin A, . Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy. Blood 2008;112:4639–4645.
   PubMed Web of Science ®Google Scholar
• Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations of AML1 are common in therapy-related myelodysplasia following therapy with alkylating agents and are significantly associated with deletion or loss of chromosome arm 7q and with subsequent leukemic transformation. Blood 2004;104:1474–1481.
   PubMed Web of Science ®Google Scholar
• Harada H, Harada Y, Niimi H, . High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia. Blood 2004;103:2316–2324.
   PubMed Web of Science ®Google Scholar
• Chen CY, Lin LI, Tang JL, . RUNX1 gene mutation in primary myelodysplastic syndrome—the mutation can be detected early at diagnosis or acquired during disease progression and is associated with poor outcome. Br J Haematol 2007;139:405–414.
   PubMed Web of Science ®Google Scholar
• Dicker F, Haferlach C, Sundermann J, . Mutation analysis for RUNX1, MLL-PTD, FLT3-ITD, NPM1 and NRAS in 269 patients with MDS or secondary AML. Leukemia 2010;24:1528–1532.
   PubMed Web of Science ®Google Scholar
• Chou WC, Hou HA, Chen CY, . Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation. Blood 2010;115:2749–2754.
   PubMed Web of Science ®Google Scholar
• Bacher U, Haferlach T, Kern W, . A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica 2007;92:744– Christiansen DH, Andersen MK, Desta F, et al. Mutations of genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal transduction pathway in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2005;19:2232–2240.
   PubMed Web of Science ®Google Scholar
• Christiansen DH, Andersen MK, Desta F, . Mutations of genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal transduction pathway in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2005;19:2232–2240.
   PubMed Web of Science ®Google Scholar
• Shih LY, Huang CF, Wang PN, . Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia. Leukemia 2004;18:466–475.
   PubMed Web of Science ®Google Scholar
• Paquette RL, Landaw EM, Pierre RV, . N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome. Blood 1993;82:590–599.
   PubMed Web of Science ®Google Scholar
• Constantinidou M, Chalevelakis G, Economopoulos T, . Codon 12 ras mutations in patients with myelodysplastic syndrome:incidence and prognostic value. Ann Hematol 1997;74:11–14.
   PubMed Web of Science ®Google Scholar
• Horiike S, Kita-Sasai Y, Nakao M, . Configuration of the TP53 gene as an independent prognostic parameter of myelodysplastic syndrome. Leuk Lymphoma 2003;44:915–922.
   PubMed Web of Science ®Google Scholar
• Kaneko H, Misawa S, Horiike S, . TP53 mutations emerge at early phase of myelodysplastic syndrome and are associated with complex chromosomal abnormalities. Blood 1995;85:2189–2193.
   PubMed Web of Science ®Google Scholar
• Haferlach C, Dicker F, Herholz H, . Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype. Leukemia 2008;22:1539–1541.
   PubMed Web of Science ®Google Scholar
• Sato Y, Suto Y, Pietenpol J, . TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies. Blood 1995;86:1525–1533.
   PubMed Web of Science ®Google Scholar
• Dunbar AJ, Gondek LP, O'Keefe CL, . 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res 2008; 68:10349–10357.
   PubMed Web of Science ®Google Scholar
• Grand FH, Hidalgo-Curtis CE, Ernst T, . Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 2009;113:6182–6192.
   PubMed Web of Science ®Google Scholar
• Slape C, Hartung H, Lin YW, . Retroviral insertional mutagenesis identifies genes that collaborate with NUP98-HOXD13 during leukemic transformation. Cancer Res 2007;67:5148–5155.
   PubMed Web of Science ®Google Scholar
• Barresi V, Palumbo GA, Musso N, . Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML. Leuk Res 2010;34:1539–1542.
   PubMed Web of Science ®Google Scholar
• Loh ML, Sakai DS, Flotho C, . Mutations in CBL occur frequently in juvenile myelomonocytic leukemia. Blood 2009;114: 1859–1863.
   PubMed Web of Science ®Google Scholar
• Niemeyer CM, Kang MW, Shin DH, . Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet 2010;42:794–800.
   PubMed Web of Science ®Google Scholar
• Xiao H, Shi J, Luo Y, . First report of multiple CEBPA mutations contributing to donor origin of leukemia relapse after allogeneic hematopoietic stem cell transplantation. Blood 2011;117: 5257–5260.
   PubMed Web of Science ®Google Scholar
• Hellstrom-Lindberg E, Cazzola M. The role of JAK2 mutations in RARS and other MDS. Hematology Am Soc Hematol Educ Program 2008:52–59.
   PubMedGoogle Scholar
• Tiacci E, Trifonov V, Schiavoni G, . BRAF mutations in hairy-cell leukemia. N Engl J Med 2011;364:2305–2315.
   PubMed Web of Science ®Google Scholar