Cryptic deletions and inversions of chromosome 21 in a phenotypically normal infant with transient abnormal myelopoiesis: a molecular cytogenetic study

Abstract

Summary.A case of transient abnormal myelopoiesis in a normal newborn without features of Down syndrome is described. The majority of bone marrow cells analysed belonged to a chromosomally abnormal clone with trisomy for chromosomes 18 and 21. Complex intrachromosomal rearrangements of one chromosome 21, demonstrated by fluorescence in situ hybridization using locus-specific probes, were found in a minor population of the clonal cells. These rearrangements involved loci previously shown to be rearranged in the leukaemic cells from patients with Down syndrome and leukaemia. However, the child's myeloproliferation resolved rapidly, with disappearance of the abnormal clone, and 3·5 years later she remains well.

Chromosome 21 abnormalities with AML1 amplification in acute lymphoblastic leukemia

“…FISH studies with probes covering different segments of the long arm of chromosome 21 showed that the marker chromosomes resulted from complex rearrangements, with uneven duplications of different regions of 21q. Cryptic complex chromosome 21 rearrangements, associated with deletions and inversions, have previously been reported in an infant with transient abnormal myelopoiesis (Kempski et al, 1998). Deletions of the distal part of one chromosome 21 including AML1 have been reported to occur in children with constitutional trisomy 21 and acute megakaryocytic leukemia (Kempski et al, 1997).…”

Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases

“…Among seven cases, two had evolved from a prior myelodysplasia. [15][16][17][18] Point mutations [19][20][21][22] and cryptic chromosome 21 rearrangements associated with deletions of AML1 23,24 have also been reported in myeloid disorders. Collectively, these observations point to possible dosage effects of AML1 in the pathogenesis of leukemia.…”

Cytogenetic and Molecular Genetic Aspects of Childhood Myeloproliferative/Myelodysplastic Disorders

“…It occurs in an estimated 10% of neonates with Down’s syndrome [60]but has been reported in normal newborns who are constitutional mosaics for trisomy 21 [62]and in infants in whom trisomy 21 is present only in the ‘leukaemic’ clone [63, 64]. TMD has also been reported in a phenotypically normal newborn infant with trisomy 18 and 21 and complex intrachromosomal rearrangements of chromosome 21 on bone marrow examination [65]. TMD is usually an incidental finding as the majority of patients are well, although most do have hepatosplenomegaly.…”

“…Tetrasomy 21, t(21;21) and i21 are the most common abnormalities seen [67]. Trisomy 12, 14 and additional +21 has been reported in 1 child [65]. Although such changes may raise the possibility of ‘true’, i.e.…”

“…Cryptic deletions of chromosome 21, confined to leukaemic cells of Down’s syndrome children with leukaemia, have been identified which suggest a loss of function of a critical gene on chromosome 21 is associated with leukaemogenesis [82]. There appears to be instability around the 21q11 locus in Down’s syndrome which may be crucial in the development of AMKL [65]although such instability was detected in very few of the clonal cells in a case of TMD. Disomic homozygosity of DNA markers in the pericentromeric 21q11 region has repeatedly been found in Down’s syndrome children with TMD and AMKL compared to Down’s syndrome children without leukaemia [83, 84, 85].…”