Specific extra chromosomes occur in a modal number dependent pattern in pediatric acute lymphoblastic leukemia.
Children with acute lymphoblastic leukemia (ALL) and high hyperdiploidy (>50 chromosomes) are considered to have a relatively good prognosis. The specific extra chromosomes are not random; extra copies of some chromosomes occur more frequently than those of others. We examined the extra chromosomes present in high hyperdiploid ALL to determine if there were a relation of the specific extra chromosomes and modal number (MN) and if the extra chromosomes present could differentiate high hyperdiploid from near-triploid and near-tetraploid cases. Karyotypes of 2,339 children with ALL and high hyperdiploidy at diagnosis showed a distinct nonrandom sequential pattern of gain for each chromosome as MN increased, with four groups of gain: chromosomes 21, X, 14, 6, 18, 4, 17, and 10 at MN 51-54; chromosomes 8, 5, 11, and 12 at MN 57-60; chromosomes 2, 3, 9,16, and 22 at MN 63-67; chromosomes 1, 7 13, 15, 19, and 20 at MN 68-79, and Y only at MN >or=80. Chromosomes gained at lower MN were retained as the MN increased. High hyperdiploid pediatric ALL results from a single abnormal mitotic division. Our results suggest that the abnormal mitosis involves specific chromosomes dependent on the number of chromosomes aberrantly distributed, raising provocative questions regarding the mitotic mechanism. The patterns of frequencies of tetrasomy of specific chromosomes differs from that of trisomies with the exception of chromosome 21, which is tetrasomic in a high frequency of cases at all MN. These results are consistent with different origins of high hyperdiploidy, near-trisomy, and near-tetrasomy.
Heerema
Nyla A
NA
Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. nyla.heerema@osumc.edu
Raimondi
Susana C
SC
Anderson
James R
JR
Biegel
Jaclyn
J
Camitta
Bruce M
BM
Cooley
Linda D
LD
Gaynon
Paul S
PS
Hirsch
Betsy
B
Magenis
R Ellen
RE
McGavran
Loris
L
Patil
Shivanand
S
Pettenati
Mark J
MJ
Pullen
Jeanette
J
Rao
Kathleen
K
Roulston
Diane
D
Schneider
Nancy R
NR
Shuster
Jonathan J
JJ
Sanger
Warren
W
Sutcliffe
Maxine J
MJ
van Tuinen
Peter
P
Watson
Michael S
MS
Carroll
Andrew J
AJ
D002648:Child; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D016000:Cluster Analysis; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*