title: Nondisjunction of chromosomes leading to hyperdiploid childhood B-cell precursor acute lymphoblastic leukemia is an early event during leukemogenesis.
abstract: A hyperdiploid karyotype is found in 30% of B-cell precursor acute lymphoblastic leukemias in childhood. The time of nondisjunction of chromosomes leading to hyperdiploidy during leukemogenesis is unknown. We used the 3 clonotypic immunoglobulin heavy chain (IgH) gene rearrangements as molecular markers for each of the 3 chromosomes 14 in a case with hyperdiploid acute lymphoblastic leukemia to define the order of events-namely, somatic recombination and nondisjunction of chromosomes-during leukemia development. A partial sequence homology of the incomplete DJ(H) rearrangement with 1 of the 2 nonfunctional VDJ(H) rearrangements suggests that the doubling of chromosomes had occurred after this DJ(H) rearrangement and thus during early B-cell differentiation. The occurrence of the nondisjunction of chromosomes as well as ongoing rearrangement processes in utero were confirmed by the presence of all 3 IgH rearrangements in neonatal blood spots, providing the first evidence that hyperdiploidy formation is an early event in leukemogenesis in these leukemias.
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderspital, University of Vienna, Austria. panzer@ccri.univie.ac.at
authors.forename: E Renate
authors.initials: ER
authors.lastname: Panzer-Grümayer
authors.forename: Karin
authors.initials: K
authors.lastname: Fasching
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
authors.forename: Klaudia
authors.initials: K
authors.lastname: Hettinger
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmitt
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stöckler-Ipsiroglu
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
mesh_terms: D017668:Age of Onset; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007621:Karyotyping; D008297:Male; D011123:Polyploidy; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains