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Immunoglobulin heavy chain gene VH-D junctional diversity at diagnosis in
patients with acute lymphoblastic leukemia
GR Kitchingman
Department of Virology and Molecular Biology, St Jude Children's Research
Hospital, Memphis, TN 38101.
Acute lymphoblastic leukemia (ALL) represents the clonal outgrowth of
transformed hematopoietic progenitor cells. We have found that blast cells
in some cases of B-precursor cell ALL contain Ig heavy chain gene
rearrangements with considerable diversity at the junctions of the variable
(VH), diversity (D), and joining (JH) regions. This diversity consists of
heterogeneous nucleotide sequences at the VH-D and, less frequently, the
D-JH junctions. In two cases, different VH segments were attached to the
same D-JH rearrangement. In all cases studied there was a much higher than
expected frequency of nucleotide sequence changes in the VH segment. At
least three mechanisms may produce these changes in different cases: (1)
continuing rearrangement of the heavy chain gene, in some cases by VH
addition to a preexisting D-JH; (2) VH replacement; and (3) an
open-and-shut mechanism. These findings suggest that an active VDJ
recombinase system is present at the time of transformation in a high
percentage of ALLs. An active recombinase in the rapidly growing leukemic
cell population could lead to genomic instability.
Volume 81,
Issue 3,
pp. 775-782,
02/01/1993
Copyright © 1993 by The American Society of Hematology
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