Different clonal origin of B-Cell populations of chronic lymphocytic leukemia and large-cell lymphoma in Richter's syndrome

A. Matolcsy, P. Casali, D. M. Knowles

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Abstract

Richter's syndrome is defined as the morphologic transformation of chronic lymphocytic leukemia (CLL) into diffuse large-cell lymphoma (DLL). To determine the clonal nature of the two malignancies, we microdissected the CLL and DLL cells from a lymph node of Richter's syndrome and analyzed the sequences of the rearranged Ig V(H)-D-J(H), genes of the two lymphomas. Using the Ig V(H)-D-J(H), sequence as a marker of clonality, we delineated the clonal relationship of the CLL and DLL cells. The microdissected CLL and DLL cells productively rearranged different V(H), D, and J(H) genes, suggesting that these DLL B cells emerge as discrete elements independent of the CLL B-cell population. The productively rearranged Ig V gene sequence of the CLL clone was 100% identical to the V(H)6 germline gene, but the rearranged Ig V(H) gene of the DLL clone was somatically point-mutated based on comparison of its sequence with those of reported germline genes. In the DLL clone, the random distribution and nature of the somatic point-mutations suggests a lack of antigen selection; the identity of the somatic point-mutations in multiple independent isolates of the same B-cell clone suggests a lack of intraclonal diversity. Thus, Richter's syndrome DLL B cells are monoclonal and can emerge as discrete elements independent of the preexisting CLL cells; antigen selection and clonal diversification are not necessarily associated with the events leading to this aggressive neoplastic transformation.

Original languageEnglish
Pages (from-to)496-503
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume764
Publication statusPublished - 1995

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Lymphoma, Large B-Cell, Diffuse
B-Cell Chronic Lymphocytic Leukemia
Lymphoma
Clone cells
Genes
Cells
Population
Clone Cells
Immunoglobulin Genes
B-Cell Lymphoma
Point Mutation
Antigens
Syndrome
B-Lymphocytes
Lymph Nodes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Different clonal origin of B-Cell populations of chronic lymphocytic leukemia and large-cell lymphoma in Richter's syndrome",
abstract = "Richter's syndrome is defined as the morphologic transformation of chronic lymphocytic leukemia (CLL) into diffuse large-cell lymphoma (DLL). To determine the clonal nature of the two malignancies, we microdissected the CLL and DLL cells from a lymph node of Richter's syndrome and analyzed the sequences of the rearranged Ig V(H)-D-J(H), genes of the two lymphomas. Using the Ig V(H)-D-J(H), sequence as a marker of clonality, we delineated the clonal relationship of the CLL and DLL cells. The microdissected CLL and DLL cells productively rearranged different V(H), D, and J(H) genes, suggesting that these DLL B cells emerge as discrete elements independent of the CLL B-cell population. The productively rearranged Ig V gene sequence of the CLL clone was 100{\%} identical to the V(H)6 germline gene, but the rearranged Ig V(H) gene of the DLL clone was somatically point-mutated based on comparison of its sequence with those of reported germline genes. In the DLL clone, the random distribution and nature of the somatic point-mutations suggests a lack of antigen selection; the identity of the somatic point-mutations in multiple independent isolates of the same B-cell clone suggests a lack of intraclonal diversity. Thus, Richter's syndrome DLL B cells are monoclonal and can emerge as discrete elements independent of the preexisting CLL cells; antigen selection and clonal diversification are not necessarily associated with the events leading to this aggressive neoplastic transformation.",
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T1 - Different clonal origin of B-Cell populations of chronic lymphocytic leukemia and large-cell lymphoma in Richter's syndrome

AU - Matolcsy, A.

AU - Casali, P.

AU - Knowles, D. M.

PY - 1995

Y1 - 1995

N2 - Richter's syndrome is defined as the morphologic transformation of chronic lymphocytic leukemia (CLL) into diffuse large-cell lymphoma (DLL). To determine the clonal nature of the two malignancies, we microdissected the CLL and DLL cells from a lymph node of Richter's syndrome and analyzed the sequences of the rearranged Ig V(H)-D-J(H), genes of the two lymphomas. Using the Ig V(H)-D-J(H), sequence as a marker of clonality, we delineated the clonal relationship of the CLL and DLL cells. The microdissected CLL and DLL cells productively rearranged different V(H), D, and J(H) genes, suggesting that these DLL B cells emerge as discrete elements independent of the CLL B-cell population. The productively rearranged Ig V gene sequence of the CLL clone was 100% identical to the V(H)6 germline gene, but the rearranged Ig V(H) gene of the DLL clone was somatically point-mutated based on comparison of its sequence with those of reported germline genes. In the DLL clone, the random distribution and nature of the somatic point-mutations suggests a lack of antigen selection; the identity of the somatic point-mutations in multiple independent isolates of the same B-cell clone suggests a lack of intraclonal diversity. Thus, Richter's syndrome DLL B cells are monoclonal and can emerge as discrete elements independent of the preexisting CLL cells; antigen selection and clonal diversification are not necessarily associated with the events leading to this aggressive neoplastic transformation.

AB - Richter's syndrome is defined as the morphologic transformation of chronic lymphocytic leukemia (CLL) into diffuse large-cell lymphoma (DLL). To determine the clonal nature of the two malignancies, we microdissected the CLL and DLL cells from a lymph node of Richter's syndrome and analyzed the sequences of the rearranged Ig V(H)-D-J(H), genes of the two lymphomas. Using the Ig V(H)-D-J(H), sequence as a marker of clonality, we delineated the clonal relationship of the CLL and DLL cells. The microdissected CLL and DLL cells productively rearranged different V(H), D, and J(H) genes, suggesting that these DLL B cells emerge as discrete elements independent of the CLL B-cell population. The productively rearranged Ig V gene sequence of the CLL clone was 100% identical to the V(H)6 germline gene, but the rearranged Ig V(H) gene of the DLL clone was somatically point-mutated based on comparison of its sequence with those of reported germline genes. In the DLL clone, the random distribution and nature of the somatic point-mutations suggests a lack of antigen selection; the identity of the somatic point-mutations in multiple independent isolates of the same B-cell clone suggests a lack of intraclonal diversity. Thus, Richter's syndrome DLL B cells are monoclonal and can emerge as discrete elements independent of the preexisting CLL cells; antigen selection and clonal diversification are not necessarily associated with the events leading to this aggressive neoplastic transformation.

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