Combination of classical and interphase cytogenetics to investigate the biology of myeloid disorders: detection of masked monosomy 7 in AML.

Numerical abnormalities of chromosome 7 were detected by using fluorescence labeled in situ hybridization (FISH) procedure with a centromere-specific probe in four cases of acute myeloid leukemia (AML) and three cases of myelodysplastic syndromes (MDS). Comparison of these results with classical cytogenetic (CC) data demonstrated a good correlation between the two methods. FISH confirmed the finding of monosomy 7 in all patients who demonstrated this abnormality by CC. Two AML patients who did not show monosomy 7 by CC were unexpectedly found to contain this abnormality in 39.8% and 17% cells when examined by FISH. Given that our modified FISH method consistently yielded > 96% hybridization efficiency, these findings constitute an unexpected but real presence of monosomy 7 in a substantial number of interphase cells that had remained undetected by classical karyotyping. Finally, a number of maturing myeloid cells including granulocytes also demonstrated monosomy 7 by FISH, thereby confirming the ability of malignant cells to undergo differentiation. We conclude that FISH constitutes a highly sophisticated molecular technique which can be extremely useful in select cases for detecting 'masked monosomy 7' as well as helping to determine the lineage of terminally mature cells in AML, thereby providing a handle on the effects of cytokines or chemotherapy on normal vs leukemic clones.