Fluorescence in situ hybridization analysis of minute marker chromosomes in leukemia with monosomy 7.

Monosomy 7 was detected in bone marrow cells from three patients, one with myeloid leukemia, and two others with myelodysplastic syndrome following previous chemotherapy. Fluorescence in situ hybridization (FISH), carried out with an alphoid DNA probe specific for chromosome 7 centromere, showed that a small marker chromosome present in the tumor cells' karyotype of the three patients, was derived from the missing chromosome 7. In two cases, the marker was a ring chromosome, whereas in the third case it was a tiny dot-like chromosome, unnoticed at first examination on R-banded metaphases. In the three cases, the marker was lost in a proportion of tumor cells. FISH experiments suggested that the marker centromere had undergone structural alterations, with a fluorescence pattern distinct from a normal one. On the whole, these data suggest that: firstly, leukemia-associated monosomy 7 results, in a proportion of cases, from a structural event rather than from simple loss of a whole chromosome 7; secondly, interpretation of interphase FISH must be cautious in monosomy 7 evaluation; and thirdly structural alteration of the chromosome 7 derivative alphoid DNA could explain its propensity to segregate unequally and to be lost at mitosis.