Micronuclei and Nuclear Abnormalities Observed in Erythroblasts in Myelodysplastic Syndromes and in de novo Acute Leukemia after Treatment

Abstract

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.