The frequencies of erythroblasts with micronuclei (EBM) and erythroblasts with aberrant nuclear shapes (EBAN) in bone marrow were evaluated in 60 patients with untreated myelodysplastic syndrome (MDS), and also in 21 patients with acute leukemia before and after treatment, and the results were compared regarding cytogenetic patterns. In patients with acute leukemia, the frequencies of EBM and EBAN in bone marrow were 0.60 ± 0.35% (mean ± SD) and 1.2 ± 1.1% before treatment, respectively, the former of which was higher than those obtained from 93 patients with various nonmalignant diseases (p < 0.01). After treatment with antileukemic drugs, the mean values of them significantly increased 9.7 and 6.1 times from the pretreatment ones, respectively. No correlation was found between the yields of EBM and EBAN and cytogenetic patterns, although regimens including administration of vincristine seemed to cause them more frequently. Most patients with MDS showed a consistent increase of EBM and EBAN at the time of diagnosis irrespective of the treatment; the mean frequencies were 7.7 and 6.3 times higher than those obtained from patients with nonmalignant diseases, respectively. Furthermore, the numbers of EBM and EBAN were significantly higher in patients with an abnormal karyotype than those with a normal karyotype (p < 0.05 for EBM and p < 0.001 for EBAN). In particular, 8 patients with a monosomy 7q showed a marked increase of EBAN (4.7 ± 4.4%) and EBAN (13 ± 6.5%). These findings revealed that drastic changes in the morphology of erythroblasts were characteristic features of MDS, and may reflect a disturbance in kinetochore/spindle microtubules, such as endoreduplication, c-mitosis or restitution, in addition to chromosome lagging.

1.
Heddle JA: A rapid test for chromosome damage. Mutat Res 1973;18:187–190.
2.
Schmid W: The micronucleus test. Mutat Res 1975;31:9–15.
3.
Countryman PI, Heddle JA: The production of micronuclei from chromosome aberration in irradiated cultures of human lymphocytes. Mutat Res 1976;41:321–332.
4.
Salmone MF, Heddle JA: The bone marrow micronucleus assay: Rationale for a revised protocol; in de Serres FJ (ed): Chemical Mutagens, Principles and Method for their Detection. New York, Plenum Press, 1983, vol 8, pp 111–149.
5.
Abe T, Isemura T, Kikuchi Y: Micronuclei in human bone-marrow cells: Evaluation of the micronucleus test using human leukemia patients treated with antileukemic agents. Mutation 1984;130:113–120.
6.
Kass L: Bone Marrow Interpretation. Lippincott, Philadelphia, 1979, pp 9–104.
7.
Therman E: Modifications of Mitosis. Human Chromosomes. Structure, Behavior, Effects. Heidelberg, Springer, 1980, pp 30–38.
8.
Pluta AF, Mackay AM, Ainsztein AM, Goldberg IG, Earnshaw WC: The centromere: Hub of chromosome activities. Science 1995;270:1591–1594.
9.
Pennisi E: Cell division gatekeepers identified. Science 1998;279:477–478.
10.
Orr-Weaver TL, Weinberg RA: A checkpoint on the road to cancer. Nature 1998;392:223–224.
11.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C: Proposals for the classification of the syndromes. Br J Haematol 1982;51:189–199.
12.
Horiike S, Taniwaki M, Misawa S, Abe T: Chromosome abnormalities and karyotypic evolutions in 83 patients with myelodysplastic syndrome and predictive values for diagnosis. Cancer 1988;62:1129–1138.
13.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Glalnick HR, Sultan C: Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British cooperative group. Ann Intern Med 1985;103:626–629.
14.
Mitelman F , Kaneko Y, Berger R: Report of the committee on chromosome changes in neoplasia; in Cuticchia AJ, Pearson PL (eds): Human Gene Mapping. A Compendium. Baltimore, Johns Hopkins University Press, 1994, pp 773–812.
15.
Brito-Babapulle F, Catovsky D, Galton DA: Clinical and laboratory features of de novo acute myeloid leukemia with trilineage myelodysplasia. Br J Haematol 1987;66:445–450.
16.
Högstedt B, Gunnar P, Nillsson PG, Mitelman F: Micronuclei in erythropoietic bone marrow cells: Relation to cytogenetic pattern and prognosis in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 1981;3:185–193.
17.
Otto AM, Paddenberg R, Schubert S, Mannherz HG: Cell-cycle arrest, micronucleus formation, and cell death in growth inhibition of MCF-7 breast cancer cells by tamoxifen and cisplatin. J Cancer Res Clin Oncol 1996;122:603–612.
18.
Raza A, Gezer S, Mundle S, Gao XZ, Alvi S, Borok R, Ritkin S, Iftikhar A, Shetty V, Parcharidou A, Loew J, Marcus B, Khan Z, Chaney C, Showel J, Gregory S, Preisler H: Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes. Blood 1995;86:268–276.
19.
Bogdanovic AD, Trpinac DP, Jankovic GM, Bumbasirevic VZ, Obradovic M, Colovic MD: Incidence and role of apoptosis in myelodysplastic syndrome: Morphological and ultrastructural assessment. Leukemia 1997;11:656–659.
20.
Raza A, Mundle S, Shetty V, Alvi S, Chopra H, Span L, Parcharidou A, Dar S, Venugopal P, Borok R, Gezer S, Showel J, Loew J, Robin E, Rifkin S, Alston D, Hernandez B, Shah R, Kaizer H, Gregory S, Preisler H: A paradigm shift in myelodysplastic syndromes. Leukemia 1996;10:1648–1652.
21.
Oftebro R , Wolf I: Mitosis of bi- and multinucleate HeLa cells. Exp Cell Res 1967;48:39–52.
22.
Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JKV, Markowitz SD, Kinzler KW, Vogelstein B: Mutations of mitotic checkpoint genes in human cancers. Nature 1998;392:300–303.
23.
Rosati S, Mick R, Xu F, Stonys E, Le Beau MM, Larson R, Vardiman JW. Refractory cytopenia with multilineage dysplasia: Further characterization of an ‘unclassifiable’ myelodysplastic syndrome. Leukemia 1996;10:20–26.
24.
Therman E, Timonen S: Multipolar spindles in human cancer cells. Hereditas 1950;36;393–405.
25.
Lind L, Sandstrom H, Wahlin A, Eriksson M, Nilsson-Sojka B, Sikstrom C, Hohmgren G: Localization of the gene for congenital dyserythropoietic anemia type III, CDAN3, to chromosome 15q21-q25. Hum Mol Genet 1995;4:109–112.
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