Skip to main content
SpringerLink
Log in

Cytogenetics of MDS

  • Chapter
  • First Online:
Myelodysplastic Syndromes

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

  • 719 Accesses

Abstract

In MDS, clonal chromosome abnormalities can be observed in 30 to >80% of patients depending on the MDS subtype and whether the disease is de novo, following an antecedent hematologic malignancy or is chemo- or radiotherapy-induced [1, 2]. In the remaining 20–70% of patients with a normal karyotype, there is a growing body of evidence that submicroscopic alterations like point mutations, microdeletions, micro amplifications, epigenetic changes or copy number neutral loss of genetic information as by uniparental disomy (UPD) constitute the genetic basis for the disease [3–5]. The cytogenetic heterogeneity in MDS is profound. In a multicentric German-Austrian study, we identified clonal karyotype changes in 1080 (52%) out of 2072 patients with MDS with a total number of 2370 clonal chromosomal abnormalities. Grouping and subdividing similar chromosomal abnormalities identified 684 different cytogenetic categories. Abnormal karyotypes showed a clear association with the severity of MDS, increasing with the medullary blast count and the intensity of cellular dysplasias [1].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Haase D, et al. 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(13):4385–95.

    Article  CAS  PubMed  Google Scholar 

  2. Leone G, Fianchi L, Voso MT. Therapy-related myeloid neoplasms. Curr Opin Oncol. 2011;23(6):672–80.

    Article  CAS  PubMed  Google Scholar 

  3. Bejar R, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Boultwood J, Wainscoat JS. Gene silencing by DNA methylation in haematological malignancies. Br J Haematol. 2007;138(1):3–11.

    Article  CAS  PubMed  Google Scholar 

  5. Mohamedali A, et al. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood. 2007;110(9):3365–73.

    Article  CAS  PubMed  Google Scholar 

  6. Ganster C, et al. Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS. Leuk Res. 2015;39(10):1079–87. https://doi.org/10.1016/j.leukres.2015.06.011.

    Article  PubMed  CAS  Google Scholar 

  7. Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, Granada I, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Valent P, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Faderl S, Pierce S, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. McGowan-Jordan J, Simons A, Schmid M. ISCN: an international system for human cytogenetic nomenclature. Basel: Karger; 2016.

    Google Scholar 

  9. Pozdnyakova O, Miron P, Tang G, et al. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities. Cancer. 2008;113:3331–40.

    Article  PubMed  Google Scholar 

  10. Solé F, Luño E, Sanzo C, et al. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica. 2005;90(9):1168–78.

    PubMed  Google Scholar 

  11. Garcia-Manero G. Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification and management. Am J Hematol. 2014;89(1):97–108.

    Article  CAS  PubMed  Google Scholar 

  12. Malcovati L, Cazzola M. The shadowlands of MDS: idiopathic cytopenias of undetermined significance (ICUS) and clonal hematopoiesis of indeterminate potential (CHIP). Hematology Am Soc Hematol Educ Program. 2015;2015:299–307.

    PubMed  Google Scholar 

  13. Malcovati L, Hellström-Lindberg E, Bowen D, et al. European Leukemia Net. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. https://doi.org/10.1182/blood-2016-03-643544.

    Article  CAS  PubMed  Google Scholar 

  16. Valcárcel D, Ademà V, Solé F, Ortega M, Nomdedeu B, Sanz G, Luño E, Cañizo C, de la Serna J, Ardanaz M, Marco V, Collado R, Grau J, Montoro J, Mallo M, Vallespí T. Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome. J Clin Oncol. 2013;31(7):916–22. https://doi.org/10.1200/JCO.2012.41.6073.

    Article  PubMed  CAS  Google Scholar 

  17. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51. https://doi.org/10.1182/blood-2009-03-209262.

    Article  CAS  PubMed  Google Scholar 

  18. Fenaux P, et al. 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;10:223–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Haferlach C, et al. Proposals for standardized protocols for cytogenetic analyses of acute leukemias, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloprolifera-tive disorders, and myelodysplastic syndromes. Genes Chromosomes Cancer. 2007;46(5):494–9.

    Article  CAS  PubMed  Google Scholar 

  20. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennet J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.

    PubMed  CAS  Google Scholar 

  21. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Della Porta MG, Malcovati L, Boveri E, Travaglino E, Pietra D, Pascutto C, Passamonti F, Invernizzi R, Castello A, Magrini U, Lazzarino M, Cazzola M. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol. 2009;27(5):754–62. https://doi.org/10.1200/JCO.2008.18.2246.

    Article  PubMed  Google Scholar 

  23. Tong WG, Quintás-Cardama A, Kadia T, Borthakur G, Jabbour E, Ravandi F, Faderl S, Wierda W, Pierce S, Shan J, Bueso-Ramos C, Kantarjian H, Garcia-Manero G. Predicting survival of patients with hypocellular myelodysplastic syndrome: development of a disease specific prognostic score system. Cancer. 2012;118(18):4462–70. https://doi.org/10.1002/cncr.27420.

    Article  PubMed  Google Scholar 

  24. Jabbour E, Takahashi K, Wang X, Megan Cornelison A, Abruzzo L, Kadia T, Borthakur G, Estrov Z, O’Brien S, Mallo M, Wierda W, Pierce S, Wei Y, Sole F, Chen R, Kantarjian H, Garcia-Manero G. Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia. Am J Hematol. 2013;88(10):831–7.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Giagounidis A, Haase D. Morphology, cytogenetics and classification of MDS. Best Pract Res Clin Haematol. 2013;26(4):337–53. https://doi.org/10.1016/j.beha.2013.09.004.

    Article  PubMed  CAS  Google Scholar 

  26. Ohyashiki JH, Ohyashiki K, Fujimura T, Kawakubo K, Shimamoto T, Iwabuchi A, Toyama K. Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes. Cancer Res. 1994;54:3557–60.

    PubMed  CAS  Google Scholar 

  27. Braulke F, et al. Molecular cytogenetic monitoring from CD34+ peripheral blood cells in myelodysplastic syndromes: first results from a prospective multicenter German diagnostic study. Leuk Res. 2013;37(8):900–6.

    Article  PubMed  Google Scholar 

  28. Platzbecker U, et al. Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study. Leukemia. 2013;27(6):1403–7. https://doi.org/10.1038/leu.2013.26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. de Oliveira FM, Miguel CE, Lucena-Araujo AR, de Lima AS, Falcão RP, Rego EM. FISH analysis for TET2 deletion in a cohort of 362 Brazilian myeloid malignancies: correlation with karyotype abnormalities. Med Oncol. 2013;30(1):483.

    Article  CAS  PubMed  Google Scholar 

  30. Ademà V, Hernández JM, Abáigar M, Lumbreras E, Such E, Calull A, Dominguez E, Arenillas L, Mallo M, Cervera J, Marugán I, Tormo M, García F, González T, Luño E, Sanzo C, Martín ML, Fernández M, Costa D, Blázquez B, Barreña B, Marco F, Batlle A, Buño I, Martínez-Laperche C, Noriega V, Collado R, Ivars D, Carbonell F, Vallcorba I, Melero J, Delgado E, Vargas MT, Grau J, Salido M, Espinet B, Melero C, Florensa L, Pedro C, Solé F. Application of FISH 7q in MDS patients without monosomy 7 or 7q deletion by conventional G-banding cytogenetics: does -7/7q- detection by FISH have prognostic value? Leuk Res. 2013;37(4):416–21. https://doi.org/10.1016/j.leukres.2012.12.010.

    Article  PubMed  CAS  Google Scholar 

  31. Lai YY, Huang XJ, Li J, Zou P, Xu ZF, Sun H, Shao ZH, Zhou DB, Chen FP, Liu ZG, Zhu HL, Wu DP, Wang C, Zhang Y, Li Y, Hou M, Du X, Wang X, Li W, Lai YR, Zhou J, Zhou YH, Fang MY, Qiu L, Wang XM, Zhang GS, Jiang M, Liang YM, Zhang LS, Chen XQ, Bai H, Lin JY. Standardized fluorescence in situ hybridization testing based on an appropriate panel of probes more effectively identifies common cytogenetic abnormalities in myelodysplastic syndromes than conventional cytogenetic analysis: a multicenter prospective study of 2302 patients in China. Leuk Res. 2015;39(5):530–5. https://doi.org/10.1016/j.leukres.2015.02.005.

    Article  PubMed  CAS  Google Scholar 

  32. Mallo M, Arenillas L, Espinet B, Salido M, Hernández JM, Lumbreras E, del Rey M, Arranz E, Ramiro S, Font P, González O, Renedo M, Cervera J, Such E, Sanz GF, Luño E, Sanzo C, González M, Calasanz MJ, Mayans J, García-Ballesteros C, Amigo V, Collado R, Oliver I, Carbonell F, Bureo E, Insunza A, Yañez L, Muruzabal MJ, Gómez-Beltrán E, Andreu R, León P, Gómez V, Sanz A, Casasola N, Moreno E, Alegre A, Martín ML, Pedro C, Serrano S, Florensa L, Solé F. Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q. Haematologica. 2008;93(7):1001–8.

    Article  PubMed  Google Scholar 

  33. Mallo MDM, Cervera J, Schanz J, Espinet B, Such E, Luno E, Steidl C, Martin ML, Germing U, Grau J, Pfeilstoecker M, Hernandez JM, Noesslinger T, Calasanz MJ, Valent P, Collado R, Fonatsch C, Bureo E, Lübbert M, Rios R, Stauder R, Arranz E, Hildebrandt B, Slovak ML, Ciguidosa J, Eclache V, Krieger O, Pedro C, Salido M, Arenillas L, Sanz G, Sanz MA, Valencia A, Florensa L, Haase D, Solé F. Prognostic impact of additional chromosomal aberrations (ACA) to 5q-in patients with primary myelodysplastic syndrome. Blood. 2008;112:582.

    Google Scholar 

  34. Braulke F, Müller-Thomas C, Götze K, Platzbecker U, Germing U, Hofmann WK, Giagounidis AA, Lübbert M, Greenberg PL, Bennett JM, Solé F, Slovak ML, Ohyashiki K, Le Beau MM, Tüchler H, Pfeilstöcker M, Hildebrandt B, Aul C, Stauder R, Valent P, Fonatsch C, Bacher U, Trümper L, Haase D, Schanz J. Frequency of del(12p) is commonly underestimated in myelodysplastic syndromes: results from a German diagnostic study in comparison with an international control group. Genes Chromosomes Cancer. 2015;54(12):809–17. https://doi.org/10.1002/gcc.22292.

    Article  PubMed  CAS  Google Scholar 

  35. Braulke F, Platzbecker U, Müller-Thomas C, Götze K, Germing U, Brümmendorf TH, Nolte F, Hofmann WK, Giagounidis AA, Lübbert M, Greenberg PL, Bennett JM, Solé F, Mallo M, Slovak ML, Ohyashiki K, Le Beau MM, Tüchler H, Pfeilstöcker M, Nösslinger T, Hildebrandt B, Shirneshan K, Aul C, Stauder R, Sperr WR, Valent P, Fonatsch C, Trümper L, Haase D, Schanz J. Validation of cytogenetic risk groups according to international prognostic scoring systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group. Haematologica. 2015;100(2):205–13.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cherry AM, Slovak ML, Campbell LJ, Chun K, Eclache V, Haase D, Haferlach C, Hildebrandt B, Iqbal AM, Jhanwar SC, Ohyashiki K, Sole F, Vandenberghe P, VanDyke DL, Zhang Y, Dewald GW. Will a peripheral blood (PB) sample yield the same diagnostic and prognostic cytogenetic data as the concomitant bone marrow (BM) in myelodysplasia? Leuk Res. 2012;36(7):832–40.

    Article  PubMed  Google Scholar 

  37. Coleman JF, Theil KS, Tubbs RR, Cook JR. Diagnostic yield of bone marrow and peripheral blood FISH panel testing in clinically suspected myelodysplastic syndromes and/or acute myeloid leukemia: a prospective analysis of 433 cases. Am J Clin Pathol. 2011;135(6):915–20.

    Article  PubMed  Google Scholar 

  38. Costa D, Valera S, Carrió A, Arias A, Muñoz C, Rozman M, et al. Do we need to do fluorescence in situ hybridization analysis in myelodysplastic syndromes as often as we do? Leuk Res. 2010;34:1437–41.

    Article  PubMed  Google Scholar 

  39. Jiang H, Xue Y, Wand Q, Pan J, Wu Y, Zhang J, et al. The utility of fluorescence in situ hybridization analysis in diagnosing myelodysplastic syndromes is limited to cases with karyotype failure. Leuk Res. 2012;36:448–52.

    Article  CAS  PubMed  Google Scholar 

  40. Kwon WK, Lee JY, Mun YC, Seong CM, Chung WS, Huh J. Clinical utility of FISH analysis in adition to G-banded karyotype in hematologic malignancies and proposal of practical research. Korean J Hematol. 2010;45:171–6.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Pinheiro RF, Chauffaille MLLF. Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities during the evolution of myelodysplastic syndrome. Braz J Med Biol Res. 2009;42:1110–2.

    Article  CAS  PubMed  Google Scholar 

  42. Pitchford CW, Hettinga AC, Reichard KK. Fluorescence in situ hybridization testing for -5/5q-, -7/7q-, +8, and del(20q) in primary myelodysplastic syndrome correlates with conventional cytogenetics in the setting of an adequate study. Am J Clin Pathol. 2010;133:260–4.

    Article  PubMed  Google Scholar 

  43. Vehmeyer K, Haase D, Alves F. Increased peripheral stem cell pool in MDS: an indication of disease progression? Leuk Res. 2001;25:955–9.

    Article  CAS  PubMed  Google Scholar 

  44. Haase D, Feuring-Buske M, Könemann S, Fonatsch C, Troff C, Verbeek W, Pekrun A, Hiddemann W, Wörmann B. Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations. Blood. 1995;86(8):2906–12.

    PubMed  CAS  Google Scholar 

  45. Haase D, Feuring-Buske M, Schäfer C, Schoch C, Troff C, Gahn B, Hiddemann W, Wörmann B. Cytogenetic analysis of CD34+ subpopulations in AML and MDS characterized by the expression of CD38 and CD117. Leukemia. 1997;11:674–9.

    Article  CAS  PubMed  Google Scholar 

  46. Braulke F, Schanz J, Jung K, Shirneshan K, Schulte K, Schuetze C, Steffens R, Truemper L, Haase D. FISH analysis of circulating CD34+ cells as a new tool for genetic monitoring in MDS: verification of the method and application to 27 MDS patients. Leuk Res. 2010;34(10):1296–301. https://doi.org/10.1016/j.leukres.2010.01.010.

    Article  PubMed  CAS  Google Scholar 

  47. Schuler E, Giagounidis A, Haase D, Shirneshan K, Büsche G, Platzbecker U, et al. Results of a multicenter prospective phase II trial investigating the safety and efficacy of lenalidomide in patients with myelodysplastic syndromes with isolated del(5q) (LE-MON 5). Leukemia. 2015;30(7):1580.

    Article  CAS  PubMed  Google Scholar 

  48. Bernasconi P, Klersy C, Boni M, Cavigliano PM, Giardini I, Rocca B, Zappatore R, Dambruoso I, Calvello C, Caresana M, Lazzarino M. Does cytogenetic evolution have any prognostic relevance in myelodysplastic syndromes? A study on 153 patients from a single institution. Ann Hematol. 2010;89(6):545–51. https://doi.org/10.1007/s00277-010-0927-z.

    Article  PubMed  Google Scholar 

  49. Tricot G, Boogaerts MA, De Wolf-Peeters C, Van den Berghe H, Verwilghen RL. The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations. Br J Haematol. 1985;59:659–70.

    Article  CAS  PubMed  Google Scholar 

  50. Haferlach C, Zenger M, Alpermann T, Schnittger S, Kern W, Haferlach T. Cytogenetic clonal evolution in MDS is associated with shifts towards unfavorable karyotypes according to IPSS and shorter overall survival: a study on 988 MDS patients studied sequentially by chromosome banding analysis. Blood. 2011;118:968.

    Google Scholar 

  51. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144(1):27–40. https://doi.org/10.1016/j.cell.2010.11.055.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Trost D, Hildebrandt B, Beier M, Müller N, Germing U, Royer-Pokora B. Molecular cytogenetic profiling of complex karyotypes in primary myelodysplastic syndromes and acute myeloid leukemia. Cancer Genet Cytogenet. 2006;165:51–63.

    Article  CAS  PubMed  Google Scholar 

  53. Schoch C, Kern W, Kohlmann A, Hiddemann W, Schnittger S, Haferlach T. Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological entity characterized by genomic imbalances and a specific gene expression profile. Genes Chromosomes Cancer. 2005;43:227–38.

    Article  CAS  PubMed  Google Scholar 

  54. Kulasekararaj AG, Smith AE, Mian SA, et al. TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haematol. 2013;160(5):660–72.

    Article  CAS  PubMed  Google Scholar 

  55. Volkert S, Kohlmann A, Schnittger S, et al. Association of the type of 5q loss with complex karyotype, clonal evolution, TP53 mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome. Genes Chromosomes Cancer. 2014;53(5):402–10.

    Article  CAS  PubMed  Google Scholar 

  56. Schaab R, Ganster C, Dierks S, Shirneshan K, Parra MT, Martin R, Germing U, Platzbecker U, Lange F, Kroeger N, Döhner K, Glass B, Nickelsen M, Stuhlmann R, Truemper LH, Schanz J, Bacher U, Haase D. Interdependency between TP53 mutations, cytogenetics, genetic Instability and prognosis in MDS and secondary AML. Blood. 2016;128:22.

    Google Scholar 

  57. Rücker FG, Bullinger L, Schwaenen C, Lipka DB, Wessendorf S, Frohling S, Bentz M, Miller S, Scholl C, Schlenk RF, Radlwimmer B, Kestler HA, Pollack JR, Lichter P, Döhner K, Döhner H. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol. 2006;24:3887–94.

    Article  CAS  PubMed  Google Scholar 

  58. Schanz J, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Tuechler H, Valent P, Hildebrandt B, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Kantarjian H, Germing U, Haase D, Estey E. 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(15):1963–70.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK, National Cancer Research Institute Adult Leukaemia Working Group. 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(3):354–65. https://doi.org/10.1182/blood-2009-11-254441.

    Article  PubMed  CAS  Google Scholar 

  60. Boultwood J, Wainscoat JS. Clonality in the myelodysplastic syndromes. Int J Hematol. 2001;73:411–5.

    Article  PubMed  Google Scholar 

  61. Cermák J, Belicková M, Krejcová H, Michalová K, Zilovcová S, Zemanová Z, Brezinová J, Sieglová Z. The presence of clonal cell subpopulations in peripheral blood and bone marrow of patients with refractory cytopenia with multilineage dysplasia but not in patients with refractory anemia may reflect a multistep pathogenesis of myelodysplasia. Leuk Res. 2005;29:371–9.

    Article  PubMed  Google Scholar 

  62. Galili N, Cerny J, Raza A. Current treatment options: impact of cytogenetics on the course of myelodysplasia. Curr Treat Options Oncol. 2007;8:117–28.

    Article  PubMed  Google Scholar 

  63. Nilsson L, Astrand-Grundström I, Anderson K, Arvidsson I, Hokland P, Bryder D, Kjeldsen L, Johansson B, Hellström-Lindberg E, Hast R, Jacobsen SEW. Involvement and functional impairment of the CD34+CD38-Thy-1+ hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood. 2002;100:259–67.

    PubMed  CAS  Google Scholar 

  64. Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K, Larson DE, McLellan MD, Dooling D, Abbott R, Fulton R, Magrini V, Schmidt H, Kalicki-Veizer J, O’Laughlin M, Fan X, Grillot M, Witowski S, Heath S, Frater JL, Eades W, Tomasson M, Westervelt P, DiPersio JF, Link DC, Mardis ER, Ley TJ, Wilson RK, Graubert TA. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med. 2012;366(12):1090–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Johansson B, Mertens F, Mitelman F. Primary vs, secondary neoplasia-associated chromosomal abnormalities - balanced rearrangements vs, genomic imbalances? Genes Chromosomes Cancer. 1996;16:155–63.

    Article  CAS  PubMed  Google Scholar 

  66. Mitelman F. Catalog of chromosome aberrations in cancer. 6th ed. New York: Wiley-Liss; 1998.

    Google Scholar 

  67. Steidl C, Schabla R, Germing U, Hildebrandt B, Noesslinger T, Pfeilstoecker M, Giagounidis A, Kunzmann R, Haas P, Luebbert M, Truemper L, Haase D. Sequential cytogenetic analyses of 577 patients with myelodysplastic syndromes: Correlations between initial karyotype, cytogenetic dynamics, and clinical course. Blood. 2005;106:2531.

    Google Scholar 

  68. Lai YY, Qiu JY, Zhang Y, Shi Y, He Q, Dang H, Lu DP. Clinical significance of continuous karyotyping in myelodysplastic syndromes. Zhonghua Xue Ye Xue Za Zhi. 2004;25:645–8.

    PubMed  Google Scholar 

  69. Tien HF, Wang CH, Chuang SM, Lee FY, Liu MC, Chen YC, Shen MC, Lin KH, Lin DT. Acute leukemic transformation of myelodysplastic syndrome – immunophenotypic, genotypic, and cytogenetic studies. Leuk Res. 1995;19:595–603.

    Article  CAS  PubMed  Google Scholar 

  70. White NJ, Nacheva E, Asimakopoulos FA, Bloxham D, Paul B, Green AR. Deletion of chromosome 20q in myelodysplasia can occur in a multipotent precursor of both myeloid cells and B-cells. Blood. 1994;83:2809–16.

    PubMed  CAS  Google Scholar 

  71. Ghaddar HM, Stass SA, Pierce S, Estey EH. Cytogenetic evolution following the transformation of myelodysplastic syndrome to acute myelogenous leukemia: implications on the overlap between the two diseases. Leukemia. 1994;8:1649–53.

    PubMed  CAS  Google Scholar 

  72. Horiike S, Taniwaki M, Misawa S, Abe T. Chromosome abnormalities and karyotypic evolution in 83 patients with myelodysplastic syndrome and predictive value for prognosis. Cancer. 1988;62:1129–38.

    Article  CAS  PubMed  Google Scholar 

  73. Horiike S, Misawa S, Nakai H, Kaneko H, Yokota S, Taniwaki M, Yamane Y, Inazawa J, Abe T, Kashima K. N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndromes. Leukemia. 1994;8:1331–6.

    PubMed  CAS  Google Scholar 

  74. Daniel CP, Ponting IL, Dexter TM. Growth and development of haemopoietic cells: a deterministic process? Haematol Blood Transfus. 1989;32:172–7.

    PubMed  CAS  Google Scholar 

  75. Kanamaru A, Tamura S. Application of long-term marrow cultures for studying the leukemic transformation of myelodysplastic syndromes. Leuk Lymphoma. 1993;11:345–52.

    Article  CAS  PubMed  Google Scholar 

  76. Tamura S, Kanamaru A, Takemoto Y, Kakishita E, Nagai K. Clonal evolutions during long-term cultures of bone marrow from de novo acute myeloid leukemia with trilineage myelodysplasia and with myelodysplastic remission marrow. Br J Haematol. 1993;84:219–26.

    Article  CAS  PubMed  Google Scholar 

  77. Michalová K, Cermák J, Brezinová J, Zemanová Z. Double minute chromosomes in a patient with myelodysplastic syndrome transforming into acute myeloid leukemia. Cancer Genet Cytogenet. 1999;109:76–8.

    Article  PubMed  Google Scholar 

  78. Reddy KS, Sulcova V. c-myc amplification in a preleukemia patient with trisomy 4 and double minutes: Review of the unique coexistence of these two chromosome abnormalities in acute myelogenous leukemia. Cancer Genet Cytogenet. 1997;95:206–9.

    Article  CAS  PubMed  Google Scholar 

  79. Pinheiro RF, de Sá Moreira ED, Silva MRR, Alberto FL, Chauffaille M. FLT3 internal tandem duplication during myelodysplastic syndrome follow-up: a marker of transformation to acute myeloid leukemia. Cancer Genet Cytogenet. 2008;183:89–93.

    Article  CAS  PubMed  Google Scholar 

  80. Lorenzo F, Nishii K, Mortma F, Kuwagata S, Usui E, Shiku H. Mutational analysis of the KIT gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. Leuk Res. 2006;30:1235–9.

    Article  CAS  PubMed  Google Scholar 

  81. Mori N, Morosetti R, Hoflehner E, Lübbert M, Mizoguchi H, Koeffler HP. Allelic loss in the progression of myelodysplastic syndrome. Cancer Res. 2000;60:3039–42.

    PubMed  CAS  Google Scholar 

  82. Harada S, Komatsu H, Seto M, Ni HP, Xu JH, Hayami Y, Tsuboi K, Wakita A, Nitta M, Kato T, Ueda R. Microsatellite instability is rare in the clinical course of myelodysplastic syndrome studied with DNA from fresh and paraffin embedded tissues. J Cancer Res Clin Oncol. 1998;124:231–5.

    Article  CAS  PubMed  Google Scholar 

  83. Maeck L, Haase D, Schoch C, Hiddemann W, Alves F. Genetic instability in myelodysplastic syndrome: detection of microsatellite instability and loss of heterozygosity in bone marrow samples with karyotype alterations. Br J Haematol. 2000;109:842–6.

    Article  CAS  PubMed  Google Scholar 

  84. Tasaka T, Lee S, Spira S, Takeuchi S, Hatta Y, Nagai M, Takahara J, Koeffler HP. Infrequent microsatellite instability during the evolution of the myelodysplastic syndrome to acute myelocytic leukemia. Leuk Res. 1996;20:113–7.

    Article  CAS  Google Scholar 

  85. Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D. Myelodysplastic syndromes: A scoring system with prognostic significance. Br J Haematol. 1985;59(3):425–33.

    Article  CAS  PubMed  Google Scholar 

  86. Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S, Irriguible D, San Miguel JF. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: A multivariate analysis of prognostic factors in 370 patients. Blood. 1989;74(1):395–408.

    PubMed  CAS  Google Scholar 

  87. Morel P, Hebbar M, Lai JL, Duhamel A, Preudhomme C, Wattel E, Bauters F, Fenaux P. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia. 1993;7(9):1315–23.

    PubMed  CAS  Google Scholar 

  88. Bernasconi P, Klersy C, Boni M, Cavigliano PM, Dambruoso I, Zappatore R. Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution. Am J Hematol. 2013;88(2):120–9.

    Article  PubMed  Google Scholar 

  89. Voso MT, Fenu S, Latagliata R, Buccisano F, Piciocchi A, Aloe-Spiriti MA, Venditti A. Revised international prognostic scoring system (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO prognostic scoring system: Validation by the Gruppo Romano Mielodisplasie Italian regional database. J Clin Oncol. 2013;31(21):2671–7.

    Article  PubMed  Google Scholar 

  90. Itzykson R, Thépot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Salanoubat C, Visanica S, Stamatoullas A, Isnard F, Marfaing-Koka A, de Botton S, Chelghoum Y, Taksin AL, Plantier I, Ame S, Boehrer S, Gardin C, Beach CL, Adès L, Fenaux P, Groupe Francophone des Myelodysplasies (GFM). Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403–11.

    Article  CAS  PubMed  Google Scholar 

  91. Lamarque M, Raynaud S, Itzykson R, Thepot S, Quesnel B, Dreyfus F, Rauzy OB, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Visanica S, Stamatoullas A, Fenaux P, Adès L. The revised IPSS is a powerful tool to evaluate the outcome of MDS patients treated with azacitidine: the GFM experience. Blood. 2012;120(25):5084–5.

    Article  CAS  PubMed  Google Scholar 

  92. de Witte T, Bowen D, Robin M, Malcovati L, Niederwieser D, Yakoub-Agha I, Mufti GJ, Fenaux P, Sanz G, Martino R, Alessandrino EP, Onida F, Symeonidis A, Passweg J, Kobbe G, Ganser A, Platzbecker U, Finke J, van Gelder M, van de Loosdrecht AA, Ljungman P, Stauder R, Volin L, Deeg HJ, Cutler C, Saber W, Champlin R, Giralt S, Anasetti C, Kröger N. Use of hematopoietic cell transplantation for patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2017;130:92.

    Google Scholar 

  93. Gerds AT, Gooley TA, Wilson WA, Deeg HJ. Components of the revised international prognostic scoring system and outcome after hematopoietic cell transplantation for myelodysplastic syndrome. Blood. 2013;121(19):4007–8.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Mishra A, Corrales-Yepez M, Ali NA, Kharfan-Dabaja M, Padron E, Zhang L, Epling-Burnette PK, Pinilla-Ibarz J, Lancet JE, List AF, Komrokji RS. Validation of the revised international prognostic scoring system in treated patients with myelodysplastic syndromes. Am J Hematol. 2013;88(7):566–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, Giagounidis A, Hildebrandt B, Bernasconi P, Knipp S, Strupp C, Lazzarino M, Aul C, Cazzola M. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25(23):3503–10.

    Article  PubMed  Google Scholar 

  96. Malcovati L, Della Porta MG, Strupp C, Ambaglio I, Kuendgen A, Nachtkamp K, Travaglino E, Invernizzi R, Pascutto C, Lazzarino M, Germing U, Cazzola M. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based prognostic scoring system (WPSS). Haematologica. 2011;96(10):1433–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Della Porta MG, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres MA, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D, Greenberg PL, Cazzola M. Validation of WHO classification-based prognostic scoring system (WPSS) for myelodysplastic syndromes and comparison with the revised international prognostic scoring system (IPSS-R). A study of the international working group for prognosis in myelodysplasia (IWG-PM). Leukemia. 2015;29(7):1502–13.

    Article  CAS  PubMed  Google Scholar 

  98. Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, Wierda WG, Pierce S, Estey E, Liu J, Huang X, Kantarjian H. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22(3):538–43.

    Article  CAS  PubMed  Google Scholar 

  99. Kantarjian H, O’Brien S, Ravandi F, Cortes J, Shan J, Bennett JM, Garcia-Manero G. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original international prognostic scoring system. Cancer. 2008;113(6):1351–61.

    Article  CAS  PubMed  Google Scholar 

  100. Such E, Cervera J, Costa D, Solé F, Vallespí T, Luño E, Collado R, Calasanz MJ, Hernández-Rivas JM, Cigudosa JC, Nomdedeu B, Mallo M, Carbonell F, Bueno J, Ardanaz MT, Ramos F, Tormo M, Sancho-Tello R, del Cañizo C, Gómez V, Marco V, Xicoy B, Bonanad S, Pedro C, Bernal T, Sanz GF. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica. 2011;96(3):375–83.

    Article  PubMed  Google Scholar 

  101. Such E, Germing U, Malcovati L, Cervera J, Kuendgen A, Della Porta MG, Nomdedeu B, Arenillas L, Luño E, Xicoy B, Amigo ML, Valcarcel D, Nachtkamp K, Ambaglio I, Hildebrandt B, Lorenzo I, Cazzola M, Sanz G. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood. 2013;121(15):3005–15.

    Article  CAS  PubMed  Google Scholar 

  102. Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, Grau J, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Valent P, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D. Monosomal karyotype in MDS: explaining the poor prognosis? Leukemia. 2013;27(10):1988–95.

    Article  CAS  PubMed  Google Scholar 

  103. Pfeilstöcker M, Tuechler H, Sanz G, Schanz J, Garcia-Manero G, Solé F, Greenberg PL. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016;128(7):902–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany

    Detlef Haase

  2. Department of Pediatric Hematology and Oncology, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Charikleia Kelaidi

Authors
  1. Detlef Haase
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charikleia Kelaidi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Detlef Haase .

Editor information

Editors and Affiliations

  1. Medizinische Klinik und Poliklinik 1, Universitätsklinikum Dresden Medizinische Klinik und Poliklinik 1, Dresden, Sachsen, Germany

    Uwe Platzbecker

  2. Department of Hematology, Hospital Saint Louis, Paris, France

    Pierre Fenaux

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Haase, D., Kelaidi, C. (2018). Cytogenetics of MDS. In: Platzbecker, U., Fenaux, P. (eds) Myelodysplastic Syndromes . Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-319-76879-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-76879-3_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-76878-6

  • Online ISBN: 978-3-319-76879-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation