Independent clonal origin of T- and B-cell clones in a composite lymphoma

Deane, Miriam; Amlot, Peter; Pappas, Helen; Norton, John D.

doi:10.1016/0145-2126(91)90465-6

“…Rarely, patients with B-cell CLL may develop highergrade lymphomas of T-cell lineage. Our institution and others have reported a few cases of B-cell CLL or lowgrade B-cell lymphomas in patients who subsequently developed higher-grade T-cell neoplasms [24][25][26][27]. EBV has been identified in high-grade T-cell lymphomas in other clinical settings [28,29] but has not been shown to be associated with Richter's transformation to a T-cell lymphoma in any of the cases described in the literature.…”

Section: Discussionmentioning

confidence: 71%

Epstein‐Barr virus infection in Richter's transformation

Ansell

¹

,

Li

²

,

Lloyd

³

et al. 1999

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Chronic lymphocytic leukemia (CLL) may convert to a diffuse large cell lymphoma (Richter's syndrome) over time. In occasional cases of Richter's transformation, Epstein-Barr virus (EBV) has been identified in the lymphoma cells. To evaluate the association of EBV infection with Richter's syndrome, the biopsy specimens and clinical records of 25 patients who were seen at the Mayo Clinic between 1984-1996 were retrospectively evaluated for the presence of EBV by immunoperoxidase staining for expression of EBV latent membrane protein (LMP), as well as the expression of EBV RNA and DNA in the cells by in situ hybridization. Four of the 25 patients showed evidence of EBV in the diffuse large cell lymphoma cells-three patients with a B-cell phenotype were positive for LMP, EBV DNA, and RNA; and one patient with a T-cell phenotype had positive EBV RNA in the large cell lymphoma cells. The Richter's syndrome was treated with combination chemotherapy in 15 patients, three received radiotherapy, three were followed without further therapy after a splenectomy, two died before treatment could be started, and one patient had insufficient follow-up. One patient with evidence of EBV in large cell lymphoma cells was treated with acyclovir as initial therapy. The median survival of EBV-positive patients was three months compared with nine months for EBV-negative patients, but this difference was not statistically significant (P = 0.385). Evidence for EBV infection related to Richter's transformation was present in 16% of the patients in this study and may be associated with a poorer outcome. Primary therapy with acyclovir in one patient did not seem to be beneficial and other therapeutic modalities in patients with EBV-positive Richter's transformation need to be explored. Am J. Hematol. 60:99-104, 1999.

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“…In each tumor, Ig V H DJ H cDNA were amplified by PCR using sense Ig V H gene family-specific (V1, V2, V3, V4, V5 and V6) leader primers in conjunction with an antisense consensus J H primer in independent reactions, as described [23,28,50,51]. The (unrearranged) germ-line V3-33 gene was amplified from case 1186 using the sense g27 primer (5'TTCACCTTCAGTAGCTATGGC-3') specific for the CDR1 sequence of the V3-33 [23] in conjunction with the degenerated antisense hept 3 primer [5'GGAATTC(AC)TG(AG)C-(CT)TCCCCTC(AG)CT(CG)3'] specific for the V H 3 gene heptamer recombination signal sequence [23].…”

Section: Pcr Amplification Cloning and Sequencing Of The Expressed Imentioning

confidence: 99%

Clonal evolution of B cells in transformation from low- to high-grade lymphoma

Matolcsy,

Schattner,

Knowles

et al. 1999

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An outcome of low-grade B cell non-Hodgkins's lymphomas is the transformation to high-grade diffuse large B cell lymphomas (DLBL). To investigate the mechanisms of clonal evolution in the transformation to DLBL, we performed longitudinal molecular analyses of immunoglobulin (Ig), V(H)DJ(H) gene sequences expressed in cases of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL) that transformed to DLBL. Among the neoplastic CLL and SLL cells and their respective high-grade transformants, there was no evidence for a clonotypic shift or acquired mutations in the expressed Ig V(H)DJ(H) gene segments, as further confirmed by a specific and sensitive PCR-single strand polymorphism analysis. In contrast, among the FL cells there was a high degree of intraclonal diversification with highly divergent V(H)DJ(H) gene sequences. Despite this intraclonal heterogeneity, the related DLBL expressed a collinear but unique V(H)DJ(H) gene sequence. The intraclonal genealogical tree for the FL case demonstrated that the DLBL emerged in association with unique V(H)DJ(H) gene mutational events. Among the intraclonal FL and related DLBL transformants, the nature and distribution of the Ig V(H)DJ(H) gene mutations were consistent with antigenic selection. Thus, clonal evolution in the transformation from low- to high-grade B cell lymphoma may involve distinct pathways which vary according to the cellular origin and the type of the progenitor B cell tumor.

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“…In each tumor, Ig V H DJ H cDNA were amplified by PCR using sense Ig V H gene familyspecific (V1, V2, V3, V4, V5 and V6) leader primers in conjunction with an antisense consensus J H primer in independent reactions, as described [23,28,50,51]. The (unrearranged) germ-line V3-33 gene was amplified from case 1186 using the sense g27 primer (5'TTCACCTTCAGTAGCTATGGC-3') specific for the CDR1 sequence of the V3-33 [23] in conjunction with the degenerated antisense hept 3 primer [5'GGAATTC(AC)TG(AG)C(CT)TCCCCTC(AG)CT(CG)3'] specific for the V H 3 gene heptamer recombination signal sequence [23].…”

Section: Pcr Amplification Cloning and Sequencing Of The Expressed Imentioning

confidence: 99%

Clonal evolution of B cells in transformation from low- to high-grade lymphoma

Matolcsy

¹

,

Schattner

²

,

Knowles

³

et al. 1999

View full text Add to dashboard Cite

An outcome of low-grade B cell non-Hodgkins's lymphomas is the transformation to high-grade diffuse large B cell lymphomas (DLBL). To investigate the mechanisms of clonal evolution in the transformation to DLBL, we performed longitudinal molecular analyses of immunoglobulin (Ig), V(H)DJ(H) gene sequences expressed in cases of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL) that transformed to DLBL. Among the neoplastic CLL and SLL cells and their respective high-grade transformants, there was no evidence for a clonotypic shift or acquired mutations in the expressed Ig V(H)DJ(H) gene segments, as further confirmed by a specific and sensitive PCR-single strand polymorphism analysis. In contrast, among the FL cells there was a high degree of intraclonal diversification with highly divergent V(H)DJ(H) gene sequences. Despite this intraclonal heterogeneity, the related DLBL expressed a collinear but unique V(H)DJ(H) gene sequence. The intraclonal genealogical tree for the FL case demonstrated that the DLBL emerged in association with unique V(H)DJ(H) gene mutational events. Among the intraclonal FL and related DLBL transformants, the nature and distribution of the Ig V(H)DJ(H) gene mutations were consistent with antigenic selection. Thus, clonal evolution in the transformation from low- to high-grade B cell lymphoma may involve distinct pathways which vary according to the cellular origin and the type of the progenitor B cell tumor.

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Independent clonal origin of T- and B-cell clones in a composite lymphoma

Cited by 11 publications

References 23 publications

Epstein‐Barr virus infection in Richter's transformation

Epstein‐Barr virus infection in Richter's transformation

Clonal evolution of B cells in transformation from low- to high-grade lymphoma

Clonal evolution of B cells in transformation from low- to high-grade lymphoma

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