Leukemia Research
Volume 27, Issue 3 , Pages 235-242 , March 2003

Clonal cytogenetic abnormalities in bone marrow specimens without clear morphologic evidence of dysplasia: a form fruste of myelodysplasia?

  • David P Steensma

      Affiliations

    • Department of Internal Medicine, Division of Hematology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-507-284-2511; fax: +1-507-266-4972.
    • ,
  • Gordon W Dewald

      Affiliations

    • Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, MN 55905 USA
    • ,
  • Janice M Hodnefield

      Affiliations

    • Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN 55905 USA
    • ,
  • Ayalew Tefferi

      Affiliations

    • Department of Internal Medicine, Division of Hematology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905, USA
    • ,
  • Curtis A Hanson

      Affiliations

    • Department of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo Clinic, Rochester, MN 55905 USA

Received 10 April 2002 ,Accepted 26 June 2002.

References 

  1. Sole F, Espinet B, Sanz GF, Cervera J, Calasanz MJ, Luno E, et al.  Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes, Grupo Cooperativo Espanol de Citogenetica Hematologica. Br J. Haematol. 2000;108:346–356
  2. Noel P, Tefferi A, Pierre RV, Jenkins RB, Dewald GW. Karyotypic analysis in primary myelodysplastic syndromes. Blood Rev. 1993;7:10–18
  3. Heaney ML, Golde DW. Myelodysplasia. N. Engl. J. Med. 1999;340:1649–1660
  4. Mufti GJ. Chromosomal deletions in the myelodysplastic syndrome. Leuk. Res. 1992;16:35–41
  5. Tefferi A, Mesa RA, Schroeder G, Hanson CA, Li CY, Dewald GW. Cytogenetic findings and their clinical relevance in myelofibrosis with myeloid metaplasia. Br. J. Haematol. 2001;113:763–771
  6. Dewald GW, Wright PI. Chromosome abnormalities in the myeloproliferative disorders. Semin. Oncol. 1995;22:341–354
  7. Diez-Martin JL, Graham DL, Petitt RM, Dewald GW. Chromosome studies in 104 patients with polycythemia vera. Mayo Clin. Proc. 1991;66:287–299
  8. Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N. Engl. J. Med. 1999;341:1051–1062
  9. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al.  Proposals for the classification of the myelodysplastic syndromes. Br. J. Haematol. 1982;51:189–199
  10. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al.  World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J. Clin. Oncol. 1999;17:3835–3849
  11. Ong ST, Le Beau MM. Chromosomal abnormalities and molecular genetics of non-Hodgkin’s lymphoma. Semin. Oncol. 1998;25:447–460
  12. Fonseca R, Coignet LJ, Dewald GW. Cytogenetic abnormalities in multiple myeloma. Part VIII. Hematol Oncol Clin North Am 1999;13:1169–80.
  13. Loss of the Y chromosome from normal and neoplastic bone marrows. United Kingdom Cancer Cytogenetics Group (UKCCG). Genes Chromosomes Cancer 1992;5:83–8.
  14. Herens C, Brasseur E, Jamar M, Vierset L, Schoenen I, Koulischer L. Loss of the Y chromosome in bone marrow cells: results on 1907 consecutive cases of leukaemia and preleukaemia. Clin. Lab. Haematol. 1999;21:17–20
  15. Pierre RV, Hoagland HC. Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging. Cancer. 1972;30:889–894
  16. Appelbaum FR, Barrall J, Storb R, Ramberg R, Doney K, Sale GE, et al.  Clonal cytogenetic abnormalities in patients with otherwise typical aplastic anemia. Exp. Hematol. 1987;15:1134–1139
  17. Spurbeck JL, Carlson RO, Allen JE, Dewald GW. Culturing and robotic harvesting of bone marrow, lymph nodes, peripheral blood, fibroblasts, and solid tumors with in situ techniques. Cancer Genet. Cytogenet. 1988;32:59–66
  18. Mitelman F, editor. ISCN 1995: An International System for Human Cytogenetic Nomenclature. Basel: Karger, 1995.
  19. Falini B, Flenghi L, Pileri S, Gambacorta M, Bigerna B, Durkop H, et al.  PG-M1: a new monoclonal antibody directed against a fixative-resistant epitope on the macrophage-restricted form of the CD68 molecule. Am. J. Pathol. 1993;142:1359–1372
  20. Yoon SY, Li CY, Mesa RA, Tefferi A. Bone marrow effects of anagrelide therapy in patients with myelofibrosis with myeloid metaplasia. Br. J. Haematol. 1999;106:682–688
  21. Hanson CA, Dayharsh GA, Morice WG, Hodnefield JM, Steensma DP. Clonal T-cell and immunoglobulin gene rearrangements in myelodysplastic syndromes (MDS): a morphologic and immunoperoxidase study. Leuk. Res. 2001;25:S12–S13
  22. Dunn DE, Tanawattanacharoen P, Boccuni P, Nagakura S, Green SW, Kirby MR, et al.  Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann. Intern. Med. 1999;131:401–408
  23. Steensma DP, Hanson CA, Letendre L, Tefferi A. Myelodysplasia with fibrosis: a distinct entity?. Leuk. Res. 2001;25:829–838
  24. Dewald GW, Stupca P. 154 chromosome anomalies in hematologic malignancies. Leuk. Res. 2000;24:487–489
  25. Morrison-DeLap SJ, Kuffel DG, Dewald GW, Letendre L. Unbalanced 1;7 translocation and therapy-induced hematologic disorders: a possible relationship. Am. J. Hematol. 1986;21:39–47
  26. Kikuchi A, Ohashi H, Hanada R, Yamamoto K. Myelodysplastic syndrome (MDS) with unbalanced t(1;7) after severe aplastic anemia (SAA) in childhood as a variant form of monosomy 7. Leukemia. 1998;12:2036–2038
  27. Davis MP, Dewald GW, Pierre RV, Hoagland HC. Hematologic manifestations associated with deletions of the long arm of chromosome 20. Cancer Genet. Cytogenet. 1984;12:63–71
  28. Mathew P, Tefferi A, Dewald GW, Goldberg SL, Su J, Hoagland HC, et al.  The 5q-syndrome: a single-institution study of 43 consecutive patients. Blood. 1993;81:1040–1045
  29. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al.  International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–2088
  30. La Starza R, Wlodarska I, Aventin A, Falzetti D, Crescenzi B, Martelli MF, et al.  Molecular delineation of 13q deletion boundaries in 20 patients with myeloid malignancies. Blood. 1998;91:231–237
  31. Olney HJ, Mitelman F, Johansson B, Mrozek K, Berger R, Rowley JD. Unique balanced chromosome abnormalities in treatment-related myelodysplastic syndromes and acute myeloid leukemia: report from an International Workshop. Genes Chromosomes Cancer. 2002;33:413–423
  32. Block AW, Carroll AJ, Hagemeijer A, Lm LM, van Lom K, Olney HJ, et al.  Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: report from an International Workshop. Genes Chromosomes Cancer. 2002;33:401–412
  33. Mitelman F, Johansson B, Mertens F. Mitelman. Database of chromosome aberrations in cancer, 2001.
  34. Dickstein JI, Vardiman JW. Issues in the pathology and diagnosis of the chronic myeloproliferative disorders and the myelodysplastic syndromes. Am. J. Clin. Pathol. 1993;99:513–525
  35. Kampmeier P, Anastasi J, Vardiman JW. Issues in the pathology of the myelodysplastic syndromes. Hematol. Oncol. Clin. North Am. 1992;6:501–522
  36. Greenberg P, Anderson J, de Witte T, Estey E, Fenaux P, Gupta P, et al.  Problematic WHO reclassification of myelodysplastic syndromes: members of the International MDS Study Group. J. Clin. Oncol. 2000;18:3447–3452
  37. Tricot GJ. Minimal diagnostic criteria for the myelodysplastic syndrome in clinical practice. Leuk. Res. 1992;16:5–6
  38. Lichtman MA. Myelodysplasia or myeloneoplasia: thoughts on the nosology of clonal myeloid diseases. Blood Cells Mol. Dis. 2000;26:572–581
  39. Kuffel DG, Schultz CG, Ash RC, Dewald GW. Normal cytogenetic values for bone marrow based on studies of bone marrow transplant donors. Cancer Genet. Cytogenet. 1991;55:39–48
  40. Raynaud SD, Brunet B, Chischportich M, Bayle J, Gratecos N, Pesce A, et al.  Recurrent cytogenetic abnormalities observed in complete remission of acute myeloid leukemia do not necessarily mark preleukemic cells. Leukemia. 1994;8:245–249
  41. Abruzzese E, Radford JE, Miller JS, Vredenburgh JJ, Rao PN, Pettenati MJ, et al.  Detection of abnormal pretransplant clones in progenitor cells of patients who developed myelodysplasia after autologous transplantation. Blood. 1999;94:1814–1819
  42. Yunis JJ. Recurrent chromosomal defects are found in most patients with acute non-lymphocytic leukemia. Cancer Genet. Cytogenet. 1984;11:125–137
  43. Keung YK, Pettenati MJ, Cruz JM, Powell BL, Woodruff RD, Buss DH. Bone marrow cytogenetic abnormalities of aplastic anemia. Am. J. Hematol. 2001;66:167–171
  44. Suzan F, Terre C, Garcia I, Bastie J, Baumelou E, Gluckman E, et al.  Three cases of typical aplastic anemia associated with a Philadelphia chromosome. Br. J. Haematol. 2001;112:385–387
  45. Jameel T, Anwar M, Abdi SI, Saleem M, Ahmad PA, Khattak MF. Aplastic anemia or aplastic preleukemic syndrome?. Ann. Hematol. 1997;75:189–193
  46. Narayanan MN, Geary CG, Freemont AJ, Kendra JR. Long-term follow-up of aplastic anemia. Br. J. Haematol. 1994;86:837–843
  47. Longo L, Bessler M, Beris P, Swirsky D, Luzzatto L. Myelodysplasia in a patient with preexisting paroxysmal nocturnal haemoglobinuria: a clonal disease originating from within a clonal disease. Br. J. Haematol. 1994;87:401–403
  48. van Kamp H, Smit JW, van den Berg E, Ruud Halie M, Vellenga E. Myelodysplasia following paroxysmal nocturnal haemoglobinuria: evidence for the emergence of a separate clone. Br. J. Haematol. 1994;87:399–400
  49. Jin JY, Tooze JA, Marsh JC, Matthey F, Gordon-Smith EC. Myelodysplasia following aplastic anemia-paroxysmal nocturnal haemoglobinuria syndrome after treatment with immunosuppression and G-CSF: evidence for the emergence of a separate clone. Br. J. Haematol. 1996;94:510–512
  50. Barrett J. Myelodysplastic syndrome and aplastic anemia–diagnostic and conceptual uncertainties. Leuk. Res. 2000;24:595–596
  51. Kurtin PJ, Dewald GW, Shields DJ, Hanson CA. Hematologic disorders associated with deletions of chromosome 20q: a clinicopathologic study of 107 patients. Am. J. Clin. Pathol. 1996;106:680–688
  52. Pedersen-Bjergaard J, Pedersen M, Roulston D, Philip P. Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood. 1995;86:3542–3552
  53. Tricot G, Criel A, Verwilghen RL. Thrombocytopenia as presenting symptom of preleukaemia in three patients. Scand. J. Haematol. 1982;28:243–250
  54. Menke DM, Colon-Otero G, Cockerill KJ, Jenkins RB, Noel P, Pierre RV. Refractory thrombocytopenia: a myelodysplastic syndrome that may mimic immune thrombocytopenic purpura. Am. J. Clin. Pathol. 1992;98:502–510
  55. George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al.  Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40
  56. Michels SD, Saumur J, Arthur DC, Robison LL, Brunning RD. Refractory anemia with excess of blasts in transformation hematologic and clinical study of 52 patients. Cancer. 1989;64:2340–2346
  57. Jonveaux P, Fenaux P, Berger R. Trisomy 6 as the sole chromosome abnormality in myeloid disorders. Cancer Genet. Cytogenet. 1994;74:150–152
  58. Horton YM, Johnson PR. Trisomy 14 in myeloid malignancies: report of two cases and review of the literature. Cancer Genet. Cytogenet. 2001;124:172–174
  59. Batanian JR, Slovak ML, Mohamed A, Dobin S, Luthardt FW, Keitges EA. Trisomy 15 is frequently observed as a minor clone in patients with anemia/MDS/NHL and as a major clone in patients with AML. Cancer Genet. Cytogenet. 2000;121:186–189
  60. Geddes AA, Bowen DT, Jacobs A. Clonal karyotype abnormalities and clinical progress in the myelodysplastic syndrome. Br. J. Haematol. 1990;76:194–202
  61. Kocova MJ, Sandberg AA. Major karyotypic abnormalities in a near-tetraploid erythroleukemia. Cancer Genet. Cytogenet. 1985;17:143–150
  62. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial, The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood. 1998;92:2322–2333
  63. Lunde JH, Allen EF. Interstitial 9q-deletion in a case of acute myeloid leukemia-M2 arising from a granulocytic sarcoma. Cancer Genet. Cytogenet. 1994;78:239–241
  64. Moir DJ, Jones PA, Pearson J, Duncan JR, Cook P, Buckle VJ. A new translocation, t(1;3)(p36;q21), in myelodysplastic disorders. Blood. 1984;64:553–555
  65. Mogul MJ, Brady K, Brothman AR, Adams R, Peterson FB, Beatty PG. Myelodysplastic syndrome presenting with clonal rearrangement isolated to chromosomal region 1q. Cancer Genet. Cytogenet. 1997;95:210–212
  66. Aventin A, La Starza R, Martinez C, Wlodarska I, Boogaerts M, Van den Berghe H. Involvement of MLL gene in a t(10;11)(q22;q23) and a t(8;11)(q24;q23) identified by fluorescence in situ hybridization. Cancer Genet. Cytogenet. 1999;108:48–52
  67. Werner M, Maschek H, Kaloutsi V, Choritz H, Georgii A. Chromosome analyses in patients with myelodysplastic syndromes: correlation with bone marrow histopathology and prognostic significance. Virchows Arch. A Pathol. Anat. Histopathol. 1992;421:47–52
  68. Inaba T, Hayashi Y, Hanada R, Nakashima M, Yamamoto K, Nishida T. Childhood myelodysplastic syndromes with 11p15 translocation. Cancer Genet. Cytogenet. 1988;34:41–46
  69. Chen Z, Richkind K, Roherty S, Velasco J, Lytle C, Brothman AR, et al.  A group of previously not recognized cytogenetic abnormalities in myeloid hematological malignancies. Cancer Genet. Cytogenet. 1999;113:162–165
  70. Secker-Walker LM, Moorman AV, Bain BJ, Mehta AB. Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities: EU concerted action 11q23 workshop. Leukemia. 1998;12:840–844
  71. Shi G, Weh HJ, Martensen S, Seeger D, Hossfeld DK. 3p21 is a recurrent treatment-related breakpoint in myelodysplastic syndrome and acute myeloid leukemia. Cytogenet. Cell Genet. 1996;74:295–299
  72. Benitez J, Carbonell F, Ferro T, Prieto F, Sanchez Fayos J. Cytogenetic studies in 18 patients with secondary blood disorders. Cancer Genet. Cytogenet. 1986;22:309–317
  73. Dewald GW, Brecher M, Travis LB, Stupca PJ. Twenty-six patients with hematologic disorders and X chromosome abnormalities. Frequent idic(X)(q13) chromosomes and Xq13 anomalies associated with pathologic ringed sideroblasts. Cancer Genet. Cytogenet. 1989;42:173–185
  74. Dewald GW, Pierre RV, Phyliky RL. Three patients with structurally abnormal X chromosomes, each with Xq13 breakpoints and a history of idiopathic acquired sideroblastic anemia. Blood. 1982;59:100–105

☆ Presented in abstract form at the Sixth International Symposium on Myelodysplastic Syndromes, Stockholm, Sweden, June 2001.

PII: S0145-2126(02)00161-3

Leukemia Research
Volume 27, Issue 3 , Pages 235-242 , March 2003

Article Tools