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VH gene rearrangement events can modify the immunoglobulin heavy chain
during progression of B-lineage acute lymphoblastic leukemia [see comments]
R Wasserman, M Yamada, Y Ito, LR Finger, BA Reichard, S Shane, B Lange and G Rovera
Division of Oncology, Children's Hospital of Philadelphia, PA.
The presence of multiple VHDJH joinings in upwards of 30% of acute
lymphoblastic leukemias (ALL) suggests a relative instability of the
rearranged immunoglobulin heavy chain (IgH) gene, but the mechanisms
involved are not completely understood. An investigation of the structure
of the VHDJH joinings using complementarity determining region (CDR)3
polymerase chain reaction (PCR) in 12 leukemias at both diagnosis and
relapse indicates that this instability may increase as a function of time.
In only one of seven cases in which relapse occurred within 3 years from
diagnosis was a new VHDJH joining identified and this coexisted with the
original diagnostic joining. Most strikingly, new VHDJH joinings were
identified in four of five cases in which relapse occurred more than 5
years from diagnosis. In this latter population, the instability of the
joinings was generated from VH----VH gene replacement events in two cases,
since the new joinings retained the original DJH sequences and partial N
region homology at the VHD junction, and probably in a third case from a VH
gene rearrangement to a common DJH precursor. Furthermore, in five of 23
(21.7%) additional cases studied at diagnosis, subclones were identified
that had similar modifications of the VH-N region. These data indicate that
VH gene replacement events and VH gene rearrangements to a common DJH
joining contribute to the instability of the VHDJH joining in ALL. This
phenomenon should be taken into consideration in those methodologies that
exploit IgH rearrangements for detection of minimal residual disease.
Volume 79,
Issue 1,
pp. 223-228,
01/01/1992
Copyright © 1992 by The American Society of Hematology
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