Nondisjunction of chromosomes leading to hyperdiploid childhood B-cell precursor acute lymphoblastic leukemia is an early event during leukemogenesis.
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.
Panzer-Grümayer
E Renate
ER
Children's Cancer Research Institute, St Anna Kinderspital, University of Vienna, Austria. panzer@ccri.univie.ac.at
Fasching
Karin
K
Panzer
Simon
S
Hettinger
Klaudia
K
Schmitt
Klaus
K
Stöckler-Ipsiroglu
Sylvia
S
Haas
Oskar A
OA
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*
D007143:Immunoglobulin Heavy Chains