Heterogeneity of immunoglobulin gene rearrangements in B‐cell lymphomas

Abstract

We have examined 69 B-cell non-Hodgkin's lymphomas (NHL) for rearrangements of the immunoglobulin (Ig) or T-cell antigen receptor (TCR) genes. The lymphomas were assigned to the categories of the Kiel classification and their B-cell nature was confirmed by immunostaining. Only 2 cases (with CLL) displayed clonal T beta-chain TCR gene rearrangements together with rearranged heavy- and light-chain Ig genes. The remaining 67 lymphomas had a germline beta-chain TCR-gene configuration. Three different patterns of Ig gene rearrangements were identified; (A) presence of both heavy- and light-chain rearrangements (H+L+); (B) rearrangement of heavy-chain gene only (H+L-); (C) heavy- and light-chain genes in germline configuration (H-L-). All the 45 low-grade NHLs and the 4 immunoblastic lymphomas exhibited pattern A and all had their kappa gene rearranged or deleted. Of 24 low-grade lymphomas tested, 13 (54%) had an addition rearrangement of the lambda light-chain gene. In contrast, the 19 high-grade centroblastic (cb) B-NHLs had distinct patterns of Ig-gene rearrangement: 12 with pattern A, 4 with B and 2 with C. In this group only 2 of 17 (12%) cases analyzed had evidence of lambda light-chain rearrangement whereas 12 of 18 (67%) had a kappa gene rearrangement or deletion. In one case expressing sIgM/lambda and with heavy chain Ig-rearrangement, no DNA was available for Ig light-chain analysis.

True

“…Control DNA and DNA from precursor-B-ALL patients were digested with the appropriate restriction enzymes, size-separated and blotted onto nylon membrane filters, which were hybridized with 32 dren were younger than 2 years and eight of them were infants (age Ͻ1 year). The diagnosis of ALL was made according to the FAB classification 22 and was always confirmed by the laboratory of the Dutch Childhood Leukemia Study Group.…”

“…Moreover, cross-lineage TCR gene rearrangements are rare (Ͻ5%) in mature B cell malignancies, such as chronic lymphocytic leukemias (CLL) or non-Hodgkin's lymphomas (NHL). 6,31,32 The occurrence of cross-lineage TCR gene rearrangements in precursor-B-ALL can be explained in several ways. Based on the fact that cross-lineage TCR gene rearrangements seem to be rare in normal precursor-B cells, TCR gene rearrangements may only occur in early precursor cells and the occurrence of TCR gene rearrangements in precursor-B cells may stop their further differentiation and maturation.…”

Langzeitergebnisse mit MACOP-B und Strahlentherapie bei aggressiven Non-Hodgkin-Lymphomen

“…Immunhistologie und DNA-Analyse ermöglichten die Zuordnung der Lymphome zu klonalen Entartungen der B-und T-Lymphozyten und ihrer Entwicklungsstadien. Diese Methoden wurden in die Klinik übernommen und führten zur Verbesserung der Lymphom-Diagnostik [2]. Zur gleichen Zeit wurden neue Chemotherapie-Schemata eingeführt.…”

Automated high resolution PCR fragment analysis for identification of clonally rearranged immunoglobulin heavy chain genes

“…17 Cloning and DNA sequencing Southern blot analysis Cloning of PCR products was performed as previously described. 17 Recombinant plasmids were sequenced by the Southern blot analysis of genomic DNA were performed as previously described 23 17 Criteria for sequence identity were as reported by Sanz. 2 Since the FR2A V H consensus primer binds too close in size by multiples of one codon as already observed by others.…”

“…Sixty-four of the cases had been previously analyzed by Southern hybridization with a clearly set off to advantage against the polyclonal fragment spectrum they could easily be discriminated from the polyradiolabeled J H probe for IgH gene rearrangements. 23,24 clonal background. Thus, with the approach described here we were able to identify a monoclonal junction in 18/19 (95%) of the cb-cc NHL cases even in the presence of a sigGene scanning of IgH-CDR3-PCR products nificant background of polyclonal B cells as in cases 7-9.…”