title: Formation of trisomies and their parental origin in hyperdiploid childhood acute lymphoblastic leukemia.
abstract: High hyperdiploidy, common in childhood acute lymphoblastic leukemia (ALL) with a favorable prognosis, is characterized by specific trisomies. Virtually nothing is known about its formation or pathogenetic impact. We evaluated 10 patients with ALL using 38 microsatellite markers mapped to 18 of the 24 human chromosomes to investigate the mechanisms underlying hyperdiploidy and to ascertain the parental origin of the trisomies. Based on the results, doubling of a near-haploid clone and polyploidization with subsequent losses of chromosomes could be excluded. The finding of equal allele dosage for tetrasomy 21 suggests that hyperdiploidy originates in a single aberrant mitosis, though a sequential gain of chromosomes other than 21 in consecutive cell divisions remains a possibility. Our study, the first to address experimentally the parental origin of trisomies in ALL, revealed no preferential duplication of maternally or paternally inherited copies of X, 4, 6, 9, 10, 17, 18, and 21. Trisomy 8 was of paternal origin in 4 of 4 patients (P =.125), and +14 was of maternal origin in 7 of 8 patients (P =.0703). Thus, the present results indicate that imprinting is not pathogenetically important in hyperdiploid childhood ALL, with the possible exception of the observed parental skewness of +8 and +14.
authors.affiliation: Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. kajsa.paulsson@klingen.lu.se
authors.forename: Kajsa
authors.initials: K
authors.lastname: Paulsson
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
authors.forename: Kowan Ja
authors.initials: KJ
authors.lastname: Jee
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Garwicz
authors.forename: Thoas
authors.initials: T
authors.lastname: Fioretos
authors.forename: Felix
authors.initials: F
authors.lastname: Mitelman
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004171:Diploidy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D008938:Mitosis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014314:Trisomy