TY - JOUR
T1 - V(H) gene rearrangement events can modify the immunoglobulin heavy chain during progression of B-lineage acute lymphoblastic leukemia
AU - Wasserman, R.
AU - Yamada, M.
AU - Ito, Y.
AU - Finger, L. R.
AU - Reichard, B. A.
AU - Shane, S.
AU - Lange, B.
AU - Rovera, G.
PY - 1992
Y1 - 1992
N2 - The presence of multiple V(H)DJ(H) 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 V(H)DJ(H) 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 V(H)DJ(H) joining identified and this coexisted with the original diagnostic joining. Most strikingly, new V(H)DJ(H) 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 V(H)→V(H) gene replacement events in two cases, since the new joinings retained the original DJ(H) sequences and partial N region homology at the V(H)D junction, and probably in a third case from a V(H) gene rearrangement to a common DJ(H) precursor. Furthermore, in five of 23 (21.7%) additional cases studied at diagnosis, subclones were identified that had similar modifications of the V(H)-N region. These data indicate that V(H) gene replacement events and V(H) gene rearrangements to a common DJ(H) joining contribute to the instability of the V(H)DJ(H) joining in ALL. This phenomenon should be taken into consideration in those methodologies that exploit IgH rearrangements for detection of minimal residual disease.
AB - The presence of multiple V(H)DJ(H) 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 V(H)DJ(H) 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 V(H)DJ(H) joining identified and this coexisted with the original diagnostic joining. Most strikingly, new V(H)DJ(H) 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 V(H)→V(H) gene replacement events in two cases, since the new joinings retained the original DJ(H) sequences and partial N region homology at the V(H)D junction, and probably in a third case from a V(H) gene rearrangement to a common DJ(H) precursor. Furthermore, in five of 23 (21.7%) additional cases studied at diagnosis, subclones were identified that had similar modifications of the V(H)-N region. These data indicate that V(H) gene replacement events and V(H) gene rearrangements to a common DJ(H) joining contribute to the instability of the V(H)DJ(H) joining in ALL. This phenomenon should be taken into consideration in those methodologies that exploit IgH rearrangements for detection of minimal residual disease.
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U2 - 10.1182/blood.v79.1.223.223
DO - 10.1182/blood.v79.1.223.223
M3 - Article
C2 - 1728310
AN - SCOPUS:0026609784
VL - 79
SP - 223
EP - 228
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -