COMBINED METAPHASE, INTERPHASE CYTOGENETIC, AND FLOW CYTOMETRIC ANALYSIS OF DNA CONTENT OF PEDIATRIC ACUTE LYMPHOBLASTIC-LEUKEMIA

Eleven pediatric acute lymphoid leukemia patients were investigated fo r chromosomal aneuploidy by interphase cytogenetics using chromosome s pecific (peri)centromeric probes for ail the somatic and sex chromosom es. Results were compared with metaphase cytogenetic and flow cytometr ic derived DNA aneuploidy data. Experiments performed on normal human cells using chromosome specific (peri)centromeric probes indicated tha t disomy could be recognized in a range of 89.1 +/- 2.7% (12.9)-96.8 /- 0.2% (0.9) far the somatic chromosomes and in 98.1 +/- 0.4% (1.3) f or the sex chromosomes. Using the cutoff level of the mean false monos omy and trisomy in the control cells +2 S.D., chromosome loss or gain for the somatic chromosomes could be revealed beyond a clonal ratio of 3.6-13.2% and 1.1-6.8%, respectively. The same value for the sex chro mosomes was 3.5% and 0%, respectively. In 5 of 11 patients the leukemi c cells proved to be diploid with all three methods at both gross DNA and chromosome levels. Interphase cytogenetics revealed chromosome los s or gain in all of the remaining six patients, however, the metaphase analysis indicated numerical aberration in only two patients. In one of them only the increased chromosome number could have been detected without identifying the chromosomes involved and in the other one the two methods indicated trisomy for a different chromosome. Flow cytomet ric data showed aneuploidy in three of the six aneuploid leukemia pati ents. The results suggest that interphase cytogenetics might be more a ccurate compared with flow cytometry and metaphase analysis to reveal aneuploidy. (C) 1998 Wiley-Liss, Inc.