An analysis of meiotic stage of nondisjunction and clinical characteristics in 27 children with Down syndrome and leukemia

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133576

Shugar, A ^[1]; Soukup, S ^[2]

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1. New York General Hospital, Ontario (Canada)
2. Children`s Hospital Medical Center, Cincinnati, OH (United States)

The observation that children with Down syndrome experience a significantly increased risk for leukemia was made in the 1950`s. Recent research has revealed that two specific forms of leukemia, acute non-lymphoblastic leukemia (specifically the subtype M7) and transient leukemia (TL) are preferentially associated with trisomy 21. The specific association of these leukemias with trisomy 21 has suggested to others that there may be a gene on chromosome 21 which predisposes to TL and M7 leukemia. If a recessive gene for susceptibility existed, then trisomies arising as a duplication of one parental centromere through a mitotic or meiosis II error would be expected to have a higher frequency of TL and M7 leukemia. The purpose of this study was (i) To test the models which propose that disomic homozygosity is preponderant in cases of TL and M7 leukemia in a Down syndrome population (ii) To further characterize the clinical characteristics of leukemia in the Down syndrome population. We utilized a combination of cytogenetic and DNA polymorphism analyses to determine stage of non-disjunction and parental orgin of the extra chromosome in 18 children with Down syndrome and leukemia. The DNA analyses are reported elsewhere. Among 27 cases of Down Syndrome leukemics, meiosis II or mitotic errors were seen in 4 out of 5 informative TL and M7 cases and in only 1 out of 5 cases of other leukemias. Clinical analysis revealed that the frequency of M7 leukemia is significantly higher in DS-leukemics compared to non-Down syndrome-leukemics. A case of Down syndrome TL with subsequent development of M7 leukemia was anecdotal evidence that TL and M7 leukemia may be of common clonal origin. The fact that fewer than 100% of TL and M7 leukemia cases demonstrated meiosis II or mitotic errors indicates that disomic homozygosity is not necessary for the development of these leukemias, however it may be an important factor which predisposes to TL and M7 leukemia in Down syndrome.

• OSTI ID: 133576
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANIMAL CELLS
CELL DIVISION
CENTROMERES
CHILDREN
CHROMOSOMAL ABERRATIONS
DOWNS SYNDROME
GENES
GENETICS
HUMAN CHROMOSOME 21
LEUKEMIA
NON-DISJUNCTION
PHENOTYPE