Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia

Williams, M. E.; Innes, Donald J.; Borowitz, MJ; Ma, Liang; Swerdlow, SH; Pe, Hurtubise; Brynes, RK; Chan, WC; Byrne, GE Jr; Whitcomb, CC

doi:10.1182/blood.v69.1.79.79

Cited by 80 publications

(4 citation statements)

References 47 publications

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“…The present study extends the phenotypic analysis of B-cell lymphomas of the Kiel classification to the DNA level. As was shown in previous studies (Arnold et al, 1983;Cleary et al, 1984Cleary et al, , 1985Williams et al, 1987;Henni et al, 1988;Rudders et al, 1988;Cossman et al, 1988) detection of heavy-and light-chain Ig-gene rearrangements represented extremely sensitive and specific markers for lineage and clonality in our series of 45 low-grade and 24 high-grade non-Hodgkin's lymphomas. We confirmed the morphological and immunohistological diagnosis of the 45 low-grade NHLs with the detection of either heavy-or light-chain rearrangements in every case.…”

Section: Discussionsupporting

confidence: 84%

“…A prerequisite for the clinical use of this objective and sensitive method is predictable correlation between Ig rearrangement patterns and phenotypic diagnosis of B-cell lymphomas. Most B-cell lymphomas derive from a differentiated B-cell with Ig heavy-chain and Ig light-chain rearrangements and with P-chain TCR-gene segments (Tpc) in germline (Ar- nold et al, 1983;Cleary et al, 1984Cleary et al, , 1985Williams et al, 1987;Henni et al, 1988;Rudders et al, 1988). Up to 52 B-NHL were studied in one single series and analysis of the immune gene configuration appears to be a sensitive and reliable marker for clonal expansions of B-cells.…”

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confidence: 99%

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Heterogeneity of immunoglobulin gene rearrangements in B‐cell lymphomas

Kneba

Bergholz

Bolz

et al. 1990

Intl Journal of Cancer

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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.

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Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 99%

Heterogeneity of immunoglobulin gene rearrangements in B‐cell lymphomas

Kneba

Bergholz

Bolz

et al. 1990

Intl Journal of Cancer

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“…Second, although Ig and TCR genes are sensitive probes for the detection of clonal populations and the determination of cell lineage, rearrangements of the Ig genes, especially J , have been demonstrated in T-cell malignancies and nonlymphoid leukemias. Conversely, rearrangements of the TCR genes have been observed in B-cell malignancies and nonlymphoid leukemias [16][17][18][19]. Finally, there are clinically benign lymphoproliferative disorders that may show monoclonal populations by gene rearrangement studies [20].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of clonality of surface immunoglobulin light and heavy chains in malignant lymphoproliferative disorders

Batata

Shen

1993

American J Hematol

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Cell suspensions from the peripheral blood of B-chronic lymphoid leukemias (B-CLL, n = 274) and reactive lymphocytosis (RLC, n = 132) and from solid tissue samples of B-non-Hodgkin's lymphoma (B-NHL, n = 466) and reactive lymphadenopathy (RLA, n = 324) were analyzed to evaluate the diagnostic value of clonality of L- and H- chains in B-CLL and B-NHL. Cutoff levels for monoclonal L-chain (mono-L) and monoclonal H-chain (mono-H) were defined. In B-CLL, the association patterns of L- and H- chains were as follows: mono-L/mono-H, 245 cases (89.42%); mono-L/polyclonal H chain (poly-H), 4 (1.46%); polyclonal L chain (poly-L)/mono-H, 2 (0.73%); poly-L/poly-H, 2 (0.73%); undetected (und)-L/mono-H, 6 (2.19%); and und-L/und-H, 15 (5.47%). In B-NHL, the association patterns were mono-L/mono-H, 433 cases (92.92%); mono-L/poly-H, 4 (0.86%); poly-L/mono-H, 8 (1.72%); poly-L/poly-H, 2 (0.43%); und-L/mono-H, 4 (0.86%); and und-L/und-H, 15 (3.22%). Monoclonality of H chains are complementary to L-chain restriction, especially in the cases with poly-L or und-L, and should be considered as a positive criterion in determining surface immunoglobulin (SIg) clonality. Monoclonality of SIg assessed by both L and H chains is both sensitive and specific for the diagnosis of B-CLL and B-NHL, and their differentiation from RLC and RLA, since none of the cases of RLC and RLA showed monoclonal SIg.

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“…gene-rearrangement technique versus phenotyping (2- 16). However, no large scale, detailed comparison has been reported.…”

Section: Introduction Materials and Methodsmentioning

confidence: 99%

Comparison of phenotyping and genotyping of lymphoid neoplasms

Sun

Eisenberg²,

Benn³

et al. 1989

Clinical Laboratory Analysis

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Comparison of phenotyping (PT) and genotyping (GT) of lymphoid neoplasms was performed on 51 specimens including lymph nodes, bone marrows, and body fluids. PT was performed with a flow cytometer using a large monoclonal antibody panel. GT included the testing for gene rearrangements of heavy chain, kappa and lambda light chains, and T-cell receptor beta-chain genes with DNA probes. The results obtained from these two techniques were generally compatible in terms of clonality and cell lineage. Only one case of B-cell lymphoma was not diagnosed by PT but showed gene rearrangement. For T-cell lymphoma, GT offers a more definitive diagnosis than does PT. Biclonality was demonstrated in one case of hairy cell leukemia by GT only. The rearranged band also offers a definitive clonal identification based on electrophoretic mobility. GT can detect a monoclonal population as small as 5% and can be performed on old or fresh specimens. PT requires 20% abnormal cells and a fresh specimen. It is concluded that GT is superior to PT for lymphoid tumor diagnosis, but it should be reserved as a supplementary test at this stage because of its technical complexity.

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Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia

Cited by 80 publications

References 47 publications

Heterogeneity of immunoglobulin gene rearrangements in B‐cell lymphomas

Heterogeneity of immunoglobulin gene rearrangements in B‐cell lymphomas

Diagnostic value of clonality of surface immunoglobulin light and heavy chains in malignant lymphoproliferative disorders

Comparison of phenotyping and genotyping of lymphoid neoplasms

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