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Cytogenetic findings in 179 patients with myelodysplastic syndromes

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Abstract

Cytogenetic analyses were performed on 266 bone marrow and peripheral blood samples from 179 patients with myelodysplastic syndromes (MDS). According to the FAB classification, 42 patients presented with RA, 18 with RARS, 37 with RAEB, 22 with CMML, and 29 with RAEB-T. Nine patients showed a secondary MDS (S MDS). FAB classification was not available for 22 patients. Clonal karyotype anomalies were found in 92 patients (51.4%). Complex chromosome abnormalities occurred in 17 (18.5%) of them. An evolution of the karyotype was detected in 16 cases (17.4%). Cytogenetically independent cells or cell clones were found in eight patients. Nonclonal chromosome abnormalities were uncovered in 29 (16.2%) of the 179 MDS patients. Consecutive studies were performed in 48 patients and revealed a good correlation of initial karyotype and clinical course. The most frequent single anomalies were 5q- in 29 (31.5%), −7 in 22 (23.9%), trisomy 1q in 14 (15.2%), and +8 in 13 (14.1%) of 92 patients respectively. Our cytogenetic findings are presented in detail and discussed in relation to patients' age, morphological classification, clinical course, and prognostic impact. The contribution of cytogenetic findings to the delineation of multistep pathogenesis of MDS with special emphasis to karyotype instability is demonstrated.

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References

  1. Anastasi J, Feng J, Le Beau MM, Larson RA, Rowley JD, Vardiman W (1993) Cytogenetic clonality in myelodysplastic syndromes studied with fluorescence in situ hybridization: linkage, response to growth factor therapy, and clone expansion. Blood 81:1580–1585

    PubMed  Google Scholar 

  2. Benitez J, Martinez Frejo C, Toledo C, Fayos JS, Ramos C (1987) Leukemic transformation in patients with the 5q-alteration: analysis of the behaviour of the 5q-clones in preleukemic to leukemic phases. Cancer Genet Cytogenet 26:199–207

    PubMed  Google Scholar 

  3. Bennett JM, Catovsky D, Daniehl MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C, The French-American-British (FAB) cooperative group (1982) Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51:189–199

    PubMed  Google Scholar 

  4. Billström R, Thiede T, Hansen S, Heim S, Kristoffersson U, Mandahl N, Mitelman F (1988) Bone marrow karyotype and prognosis in primary myelodysplastic syndromes. Eur J Haematol 41:341–346

    PubMed  Google Scholar 

  5. Fonatsch C, Schaadt M, Kirchner H, Diehl V (1980) A possible correlation between the degree of karyotype aberrations and the rate of sister chromatid exchanges in lymphoma lines. Int J Cancer 26:749–756

    PubMed  Google Scholar 

  6. Fonatsch C, Haase D, Freund M, Bartels H, Tesch H (1991) Partial trisomy 1q. A nonrandom primary chromosomal abnormality in myelodysplastic syndromes? Cancer Genet Cytogenet 56:243–253

    PubMed  Google Scholar 

  7. Ganser A, Hoelzer D (1992) Clinical course of myelodysplastic syndromes. Hematol Oncol Clin North Am 6:607–618

    PubMed  Google Scholar 

  8. Geddes AD, Bowen DT, Jacobs A (1990) Clonal karyotype abnormalities and clinical progress in the myelodysplastic syndrome. Br J Haematol 76:194–202

    PubMed  Google Scholar 

  9. Gough NM, Gearing DP, Nicola NA, Baker E, Pritchard M, Callen DF, Sutherland GR (1990) Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region. Nature 345:734–736

    PubMed  Google Scholar 

  10. Grier HE, Weinstein HJ, Revesz T, Houlihan PW, Greenhalgh CL, Nathan DG, Tantravahi R (1986) Cytogenetic evidence for involvement of erythroid progenitors in a child with therapy-linked myelodysplasia. Br J Haematol 64:513–519

    PubMed  Google Scholar 

  11. Groupe Francais de Cytogénétique Hématologique (1986) Cytogenetics of chronic myelomonocytic leukemia. Cancer Genet Cytogenet 21:11–30

    Google Scholar 

  12. Haase D, Fonatsch C (1990) Karyotype and in vitroresponse to GM-CSF. Analysis of bone marrow cultures in leukemia, myelodysplasia and aplastic anemia. Blut 60:192–197

    PubMed  Google Scholar 

  13. Haase D, Fonatsch C (1990) Monosomy 7 provides a proliferative andvantage for leukemic cells under incubation with GM-CSF in vitro. Blut 61:322–323

    PubMed  Google Scholar 

  14. Haase D, Fonatsch C, Freund M (1992) Karyotype instability in myelodysplastic syndromes — a specific step in pathogenesis preceding clonal chromosome anomalies. Leukemia Lymphoma 8:221–228

    PubMed  Google Scholar 

  15. Haase D, Kröger M, Fonatsch C (1993) Cytogenetics of acute leukemia following MDS. In: Büchner T et al. (eds) Acute leukemias IV. Prognostic factors. Springer, Berlin Heidelberg New York, pp 473–478

    Google Scholar 

  16. Haase D, Feuring-Buske M, Troff C, Könemann S, Hiddemann W, Wörmann B (1994) Affection of CD34-positive progenitor cells by chromosome abnormalities and karyotype evolution in a case of secondary MDS. Leuk Res 18 [Suppl]: Abstr 44

  17. Haase D, Feuring-Buske M, Könemann S, Fonatsch C, Troff C, Verbeek W, Hiddemann W, Wörmann B (1994) Cytogenetic identification of leukemia-associated abnormalities in hematopoietic stem cells of AML patients. Blood 84 [Suppl 1]: Abstr. 1217

  18. Haase D, Freund M, Welte K, Zabel K, Fonatsch C (1994) Association of monosomy 7 and leukemic response to myeloid growth factors. In: Freund M, Link, Weite (eds) Cytokines in hemopoiesis, oncology and immunology III. Springer, Berlin Heidelberg, New York, pp 254–260

    Google Scholar 

  19. Heim S, Mitelman F (1986) Chromosome abnormalities in the myelodysplastic syndromes. Clin Haematol 15:1003–1021

    PubMed  Google Scholar 

  20. Heim S, Mitelman F (1989) Cytogenetically unrelated clones in hematological neoplasms. Leukemia 3:6–8

    PubMed  Google Scholar 

  21. Hellström-Lindberg E, Robert K-H, Gahrton G, Lindberg G, Forsblom A-M, Kock Y, Öst A (1992) A predictive model for the clinical response to low-dose ara-C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia. Br J Haematol 81:503–511

    PubMed  Google Scholar 

  22. Hogge DE, Shannon KM, Kalousek DK, Schonberg S, Schaffner V, Zoger S, Eaves CJ, Eaves AC (1987) Juvenile monosomy 7 syndrome: evidence that the disease originates in a pluripotent hemopoietic stem cell. Leuk Res 11:705–709

    PubMed  Google Scholar 

  23. ISCN (1991) Guidelines for cancer cytogenetics. In: Mitelman F (ed) Supplement to an international system for human cytogenetic nomenclature. S. Karger, Basel

    Google Scholar 

  24. Iurlo A, Mecucci C, Van Orshoven A, Michaux J-L, Boogaerts M, Noens L, Bosly A, Louwagie A, Van Den Berghe H (1989) Cytogenetic and clinical investigations in 76 cases with therapyrelated leukemia and myelodysplastic syndrome. Cancer Genet Cytogenet 43:227–241

    PubMed  Google Scholar 

  25. Janssen JWG, Buschle M, Layton M, Drexler HG, Lyons J, Van Den Berghe H, Heimpel H, Kubanek B, Kleihauer E, Mufti G, Bartram C (1989) Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin. Blood 73:248–254

    PubMed  Google Scholar 

  26. Johansson B, Mertens F, Heim S, Kristoffersson U, Mitelman F (1991) Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocytic leukemia (sANLL). Eur J Haematol 47:17–27

    PubMed  Google Scholar 

  27. Jotterand-Bellomo M, Parlier V, Schmidt PM, Beris P (1990) Cytogenetic analysis of 54 cases of myelodysplastic syndrome. Cancer Genet Cytogenet 46:157–172

    PubMed  Google Scholar 

  28. Kere J, Ruutu T, De La Chapelle A (1987) Monosomy 7 in granulocytes and monocytes in myelodysplastic syndrome. N Engl J Med 316:499–503

    PubMed  Google Scholar 

  29. Knuutila S, Teerenhovi L, Borgström GH (1984) Chromosome instability is associated with hypodiploid clones in myelodysplastic syndromes. Hereditas 101:19–30

    PubMed  Google Scholar 

  30. Kobayashi H, Kaneko Y, Maseki N, Sakurai M (1990) Karyotypically unrelated clones in acute leukemias and myelodysplastic syndromes. Cancer Genet Cytogenet 47:171–178

    PubMed  Google Scholar 

  31. Koken MHM, Smit EME, Jaspers-Dekker I, Oostra BA, Hagemeijer A, Bootsma D, Hoeijmakers JHJ (1992) Localization of two human homologs, HHR6A and HHR6B, of the yeast DNA repair gene RAD6 to chromosomes Xq24-25 and 5q23-31. Genomics 12:447–453

    PubMed  Google Scholar 

  32. Kremer E, Baker E, D'Andrea RJ, Slim R, Phillips H, Moretti PAB, Lopez AF, Petit C, Vadas M, Sutherland GR, and Goodall GJ (1993) A cytokine receptor gene cluster in the X-Y pseudoautosomal region? Blood 82:22–28

    PubMed  Google Scholar 

  33. Le Beau MM, Westbrook CA, Diaz MO, Larson RA, Rowley JD, Gasson JC, Golde DW, Sherr CJ (1986) Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. Science 231:984–987

    PubMed  Google Scholar 

  34. Le Beau MM, Epstein WD, O'Brien SJ, Nienhuis AW, Yang Y-C, Clark SC, Rowley JD (1987) The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q. Proc Natl Acad Sci USA 84:5913–5917

    PubMed  Google Scholar 

  35. Le Beau MM, Lemons RL, Espinosa III R, Larson RA, Arai N, Rowley JD (1989) Interleukin-4 and interleukin-5 map to human chromosome 5 in a region encoding growth factors and receptors and are deleted in myeloid leukemias with a del(5q). Blood 73:647–650

    PubMed  Google Scholar 

  36. Mecucci C, Rege-Cambrin G, Michaux JL, Tricot G, Van Den Berghe H (1986) Multiple chromosomally distinct cell populations in myelodysplastic syndromes and their possible significance in the evolution of the disease. Br J Haematol 64:699–706

    PubMed  Google Scholar 

  37. Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28

    PubMed  Google Scholar 

  38. Nowell PC, Besa EC, Stelmach T, Finan JB (1986) Chromosome studies in preleukemic states. V. Prognostic significance of single versus multiple abnormalities. Cancer 58:2571–2575

    PubMed  Google Scholar 

  39. Parlier L, Tiainen N, Beris Ph, Miescher PA, Knuutila S, Jotterand Bellomo M (1992) Trisomy 8 detection in granulomonocytic, erythrocytic and megakaryocytic lineages by chromosomal in situ suppression hybridization in a case of refractory anaemia with ringed sideroblasts complicating the course of paroxysmal nocturnal haemoglobinuria. Br J Haematol 81:296–304

    PubMed  Google Scholar 

  40. Pierre RV, Catovsky D, Mufti GJ, Swansbury GJ, Mecucci C, Dewald GW, Ruutu T, Van Den Berghe H, Rowley JD, Mitelman F, Reeves BR, Alimena G, Garson OM, Lawler SD, de La Chapelle (1989) Clinical-cytogenetic correlations in myelodysplasia (preleukemia). Cancer Genet Cytogenet 40:149–161

    PubMed  Google Scholar 

  41. Raskind WH, Tirumali N, Jacobson R, Singer J, Fialkow PJ (1984) Evidence for a multistep pathogenesis of a myelodysplastic syndrome. Blood 63:1318–1323

    PubMed  Google Scholar 

  42. Rowley JD, Golomb HM, Vardiman JW (1981) Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. Blood 58:759–767

    PubMed  Google Scholar 

  43. Sanz GF, Sanz MA (1992) Prognostic factors in myelodysplastic syndromes. Leuk Res 16:77–86

    PubMed  Google Scholar 

  44. Solé F, Prieto T, Badia S, Woessner S, Florensa L, Caballin MR, Coll MD, Besses C, Sans-Sabrafen J (1992) Cytogenetic studies in 112 cases of untreated myelodysplastic syndromes. Cancer Genet Cytogenet 64:12–20

    PubMed  Google Scholar 

  45. Suciu S, Kuse R, Weh HJ, Hossfeld DK (1990) Results of chromosome studies and their relation to morphology, course, and prognosis in 120 patients with de novo myelodysplastic syndrome. Cancer Genet Cytogenet 44:15–26

    PubMed  Google Scholar 

  46. Taviaux SA, Demaille JG (1993) Localization of human cell cycle regulatory genes CDC25C to 5q31 and WEE1 to 11p15.3-11p15 by fluorescence in situ hybridization. Genomics 15:194–196

    PubMed  Google Scholar 

  47. Tefferi A, Thibodeau SN, Solberg LA (1990) Clonal studies in a myelodysplastic syndrome using X-linked restriction fragment length polymorphisms. Blood 75:1770–1773

    PubMed  Google Scholar 

  48. Toyama K, Ohyashiki K, Yoshida Y, Abe T, Asano S, Hirai H, Hirashima K, Hotta T, Kuramoto A, Kuriya S, Miyazaki T, Kakishita E, Mizoguchi H, Okada M, Shirakawa S, Takaku F, Tomonaga M, Uchino H, Yasunaga K, Nomura T (1993) Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan. Leukemia 7:499–508

    PubMed  Google Scholar 

  49. Tricot G, Boogaerts MA, De Wolf-Peeters C, Van Den Berghe, Verwilghen RL (1985) The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations. Br J Haematol 59:659–670

    PubMed  Google Scholar 

  50. Van den Berghe H, Vermaelen K, Mecucci C, Barbieri D, Tricot G (1985) The 5q-anomaly. Cancer Genet Cytogenet 17:189–255

    PubMed  Google Scholar 

  51. White AD, Jacobs A (1992) Peripheral blood chromosome aberrations in MDS. Cancer Genet Cytogenet 59:167–172

    PubMed  Google Scholar 

  52. Willmann CL, Sever CE, Pallavicini MG, Harada H, Tanaka N, Slovak ML, Yamamoto H, Harada K, Meeker TC, List AF, Taniguchi T (1993) Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. Science 259:968–971

    PubMed  Google Scholar 

  53. Yunis JJ, Rydell RE, Oken MM, Arnesen MA, Mayer MG, Lobell M (1986) Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes. Blood 67:1721–1730

    PubMed  Google Scholar 

  54. Yunis JJ, Lobell M, Arnesen MA, Oken MM, Mayer MG, Rydell RE, Brunning RD (1988) Refined chromosome study helps define prognostic subgroups in most patients with primary myelodysplastic syndrome and acute myelogenous leukaemia. Br J Haematol 68:189–194

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Zentrum Innere Medizin, Department of Hematology and Oncology, Georg-August-Universität, Robert-Koch-Strasse 40, D-37075, Göttingen, Germany

    D. Haase & B. Wörmann

  2. Arbeitsgruppe Tumorcytogenetik, Institut für Humangenetik, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany

    C. Fonatsch

  3. Abtl. Hämatologie und Onkologie, Medizinische Fakultät, Universität Rostock, D-18055, Rostock, Germany

    M. Freund

  4. Abtl. Hämatologie/Onkologie, Medizinische Klinik, Portastrasse 7-9, D-32423, Minden, Germany

    H. Bodenstein

  5. Abtl. Hämatologie/Onkologie, Städt. Krankenhaus Süd, Kronsforder Allee 71-73, D-23560, Lübeck, Germany

    H. Bartels

  6. Abtl. Kinderklinik, Universitätsklinikum der Gesamthochschule Essen, Hufelandstrasse 55, D-45147, Essen, Germany

    B. Stollmann-Gibbels

  7. III. Medizinische Klinik, Klinikum Mannheim, Wiesbadenerstrasse 7-11, D-68305, Mannheim, Germany

    E. Lengfelder

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  1. D. Haase
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Haase, D., Fonatsch, C., Freund, M. et al. Cytogenetic findings in 179 patients with myelodysplastic syndromes. Ann Hematol 70, 171–187 (1995). https://doi.org/10.1007/BF01700373

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  • DOI: https://doi.org/10.1007/BF01700373

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