DUPLICATION AND LOSS OF CHROMOSOME-21 IN 2 CHILDREN WITH DOWN-SYNDROME AND ACUTE-LEUKEMIA

Acute leukemia in Down syndrome (DS) is often associated with addition al changes in the number or structure of chromosome 21. We present two DS patients whose leukemic karyotypes were associated with changes in chromosome 21 ploidy. Patient 1 developed acute lymphocytic leukemia (type L1); disomy for chromosome 21 was evident in all blast cells exa mined, Loss of the paternal chromosome in the leukemic clone produced maternal uniparental disomy with isodisomy over a 25-cM interval, The second patient had acute monoblastic leukemia (type M5) with tetrasomy 21 in all leukemic cells. DNA polymorphism analysis showed duplicate paternal chromosomes in the constitutional genotype, The maternal chro mosome was subsequently duplicated in the leukemic clone. The distinct inheritance patterns of chromosome 21 in the blast cells of these pat ients would appear to indicate that leukemogenesis occurred by differe nt genetic mechanisms in each individual. (C) 1995 Wiley-Liss, Inc.