Differences in immunoglobulin heavy chain gene rearrangmeent patterns between bone marrow and blood samples in childhood precursor B-acute lymphoblastic leaukemia at diagnosis.
Bone marrow (BM) and corresponding peripheral blood (PB) samples from 30 patients with precursor B-acute lymphoblastic leukemia (precursor B-ALL) were analyzed for the configuration of their immunoglobulin (Ig) heavy chain (IgH) and Ig kappa chain (Ig kappa) genes. Rearrangements and/or delections of the IgH and Ig kappa genes were detected in 100 and 47% of patients in this series of precursor B-ALL, respectively. Multiple rearranged IgH gene bands, generally differing in density, were found in 10 precursor B-ALL samples. This multi-band pattern is most probably caused by subclone formation due to continuing rearrangement processes. In five of the 10 bi/oligoclonal cases (50%) differences in IgH gene rearrangement patterns between BM and PB samples were observed, which could be interpreted as the presence of an edeletections of the IgH and Ig kappa genestra subclone in two cases and differences in the size of the subclones in three cases. In the 20 monoclonal precursor B-ALL, no dissimilarities in IgH gene rearrangement patterns between BM and the corresponding PB samples were found. Differences in Ig kappa gene rearrangement patterns between BM and PB were not observed in this series of precursor B-ALL, which is in line with the finding that no multiple Ig kappa gene rearrangements were detectable. In all five cases, the edelections of the IgH and Ig kappa genestra subclones or the relatively larger sized subclones were found in the BM samples, suggesting that subclone formation in precursor B-ALL occurs in the tissue compartment from which the precursor B-ALL cells are thought to originate. This phenomenon will lead to underestimation of subclone formation, if only IgH gene analysis of PB samples is performed. In addition, it will hamper the detection of minimal residual disease by the polymerase chain reaction mediated amplification of 'leukemia-specific' IgH gene junctional regions, because it is unpredictable which subclone will cause minimal residual disease and/or relapse.
Beishuizen
A
A
Department of Immunology, University Hospital Dijkzigt/Erasmus University, Rotterdam, The Netherlands.
Verhoeven
M A
MA
Hählen
K
K
van Wering
E R
ER
van Dongen
J J
JJ
D001856:Bone Marrow Examination; D002648:Child; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000473:pathology