Home LiteratureArticle Details
PMID: 1898660 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Histologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell.

The Journal of experimental medicine ·Vol. 173 ·No. 1 ·1991-01-01 ·Pages 197-207

Zelenetz AD, Chen TT, Levy R

Abstract

To investigate the clonal relationship between follicular lymphoma (FL) and transformed diffuse lymphoma (tDL), we examined the expression of tumor idiotype, immunoglobulin (Ig) gene rearrangements and sequence of Ig variable genes in paired tissue specimens. All 16 cases analyzed expressed surface immunoglobulin (sIg) on both the FL and the tDL, though the immunophenotype of one case of FL could not be definitively determined. In 14 of 15 cases, the surface immunophenotype was preserved; the exception was likely secondary to a class switch from IgM to IgG. In 12 of 13 cases, antiidiotypic monoclonal antibodies prepared against the FL reacted with the paired tDL. Analysis of Ig gene rearrangements in four cases by Southern blot hybridization showed evidence of clonal relationships in all cases though concordance was not seen with all probes tested (C kappa, C lambda, JH, PFL1, and PFL2). In the one case that had a discordant L chain rearrangement, sequence analysis of the L chain demonstrated a common mature B cell origin for both the FL and tDL. To determine whether tDL arose from one or more FL cells, the sequences of the H chain variable genes were analyzed. Individual clones of the V region gene of the FL showed a random distribution of changes throughout the sequence. In contrast, individual clones of the V region gene from tDL shared numerous nonrandom sequence alterations, implying a common single cell origin. In conclusion, tDL is a mature B cell and arises by transformation of a single FL cell.

MeSH Terms
Antibodies, Anti-Idiotypic Antibodies, Monoclonal Base Sequence Blotting, Southern Cell Transformation, Neoplastic/immunology Clone Cells Humans Immunoglobulin Heavy Chains/genetics Immunoglobulin Light Chains/genetics Immunoglobulin Variable Region/genetics Lymphoma, B-Cell/genetics,immunology,pathology Lymphoma, Follicular/genetics,immunology,pathology Lymphoma, Non-Hodgkin/etiology,genetics,immunology Molecular Sequence Data
Chemicals
Antibodies, Anti-Idiotypic Antibodies, Monoclonal Immunoglobulin Heavy Chains Immunoglobulin Light Chains Immunoglobulin Variable Region
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zelenetz A D
Department of Medicine, Stanford Medical School, California 94305.
Chen T T
Levy R
References (45)
45 references, click to expand
  1. Autoantibody-associated kappa light chain variable region gene expressed in chronic lymphocytic leukemia with little or no somatic mutation. Implications for etiology and immunotherapy.
    J Exp Med. 1988 Mar 1;167(3):840-52 PMID: 3127527
  2. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  3. Lack of detectable somatic hypermutation in the V region of the Ig H chain gene of a human chronic B lymphocytic leukemia.
    J Immunol. 1988 Dec 1;141(11):3994-8 PMID: 3141510
  4. Antibody engineering for the analysis of affinity maturation of an anti-hapten response.
    EMBO J. 1988 Jul;7(7):1995-2001 PMID: 3138111
  5. Clustering of extensive somatic mutations in the variable region of an immunoglobulin heavy chain gene from a human B cell lymphoma.
    Cell. 1986 Jan 17;44(1):97-106 PMID: 3079673
  6. Regulation of the assembly and expression of variable-region genes.
    Annu Rev Immunol. 1986;4:339-68 PMID: 3085692
  7. Mutational hot spots in Ig V region genes of human follicular lymphomas.
    J Exp Med. 1988 Aug 1;168(2):475-89 PMID: 3045247
  8. High efficiency transformation of E. coli by high voltage electroporation.
    Nucleic Acids Res. 1988 Jul 11;16(13):6127-45 PMID: 3041370
  9. Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma.
    N Engl J Med. 1988 May 26;318(21):1373-8 PMID: 3285208
  10. Clonal recruitment and somatic mutation in the generation of immunological memory to the hapten NP.
    EMBO J. 1986 Oct;5(10):2459-68 PMID: 2430792
  11. Alterations in immunoglobulin genes reveal the origin and evolution of monotypic and bitypic B cell lymphomas.
    Am J Pathol. 1989 Jun;134(6):1233-42 PMID: 2547318
  12. Activity of DNA modification and restriction enzymes in KGB, a potassium glutamate buffer.
    Gene Anal Tech. 1988 Sep-Oct;5(5):105-7 PMID: 2903843
  13. Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene.
    Proc Natl Acad Sci U S A. 1988 Nov;85(22):8548-52 PMID: 3186743
  14. Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.
    EMBO J. 1988 Mar;7(3):727-38 PMID: 3396540
  15. Retention of an idiotypic determinant in a human B-cell lymphoma undergoing immunoglobulin variable-region mutation.
    Proc Natl Acad Sci U S A. 1987 Jul;84(14):5053-7 PMID: 3496601
  16. A clinical trial of anti-idiotype therapy for B cell malignancy.
    Blood. 1985 Jun;65(6):1349-63 PMID: 3888313
  17. Preferential utilization of conserved immunoglobulin heavy chain variable gene segments during human fetal life.
    Proc Natl Acad Sci U S A. 1990 Aug;87(16):6146-50 PMID: 2117273
  18. Evolution of human immunoglobulin kappa J region genes.
    J Biol Chem. 1982 Feb 10;257(3):1516-22 PMID: 6276389
  19. Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments.
    Cell. 1980 Nov;22(1 Pt 1):197-207 PMID: 6775818
  20. The immunologic phenotyping of bone marrow biopsies and aspirates: frozen section techniques.
    Blood. 1982 May;59(5):913-22 PMID: 7042005
  21. Histologic progression in non-Hodgkin's lymphoma.
    Blood. 1982 Feb;59(2):258-64 PMID: 7034812
  22. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  23. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  24. A simple and very efficient method for generating cDNA libraries.
    Gene. 1983 Nov;25(2-3):263-9 PMID: 6198242
  25. An autopsy study of histologic progression in non-Hodgkin's lymphomas. 192 cases from the National Cancer Institute.
    Cancer. 1983 Aug 1;52(3):393-8 PMID: 6344979
  26. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  27. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.
    Cell. 1981 Dec;27(3 Pt 2):583-91 PMID: 6101209
  28. Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma.
    J Clin Invest. 1989 Nov;84(5):1454-9 PMID: 2509518
  29. Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production.
    J Exp Med. 1989 Mar 1;169(3):613-24 PMID: 2538543
  30. Follicular low-grade non-Hodgkin's lymphoma: long-term outcome with or without tumor progression.
    Eur J Haematol. 1989 Feb;42(2):155-63 PMID: 2917634
  31. Progression of follicular large cell lymphoma to Burkitt's lymphoma.
    Cancer. 1989 Feb 15;63(4):700-2 PMID: 2644011
  32. Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease.
    Proc Natl Acad Sci U S A. 1988 Jul;85(13):4869-73 PMID: 3133663
  33. Pre-B-cell leukemia with a t(8; 14) and a t(14; 18) translocation is preceded by follicular lymphoma.
    Oncogene. 1988 May;2(5):431-5 PMID: 3131717
  34. Absence of Ig V region gene somatic hypermutation in advanced Burkitt's lymphoma.
    J Immunol. 1989 Jul 15;143(2):692-8 PMID: 2500485
  35. The presence of clonogenic cells in high-grade malignant lymphoma: a prognostic factor.
    Blood. 1987 May;69(5):1307-14 PMID: 3567358
  36. Organization of human immunoglobulin heavy chain diversity gene loci.
    EMBO J. 1988 Dec 20;7(13):4141-50 PMID: 3243276
  37. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18.
    Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439-43 PMID: 2865728
  38. Continuing rearrangement but absence of somatic hypermutation in immunoglobulin genes of human B cell precursor leukemia.
    J Exp Med. 1988 Jul 1;168(1):229-45 PMID: 2840480
  39. Detection of a second t(14;18) breakpoint cluster region in human follicular lymphomas.
    J Exp Med. 1986 Jul 1;164(1):315-20 PMID: 3014037
  40. Frequent biclonality and Ig gene alterations among B cell lymphomas that show multiple histologic forms.
    J Exp Med. 1985 Apr 1;161(4):850-63 PMID: 2984307
  41. Clustered arrangement of immunoglobulin lambda constant region genes in man.
    Nature. 1981 Dec 10;294(5841):536-40 PMID: 6273747
  42. Directional cloning of cDNA using a selectable SfiI cassette.
    Gene. 1990 Apr 30;89(1):123-7 PMID: 2165017
  43. Strategies for production of monoclonal anti-idiotype antibodies against human B cell lymphomas.
    J Immunol. 1984 Jul;133(1):495-501 PMID: 6609992
  44. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma.
    Proc Natl Acad Sci U S A. 1984 Jan;81(2):593-7 PMID: 6607475
  45. Alternative V kappa gene rearrangements in a murine B cell lymphoma. An explantation for idiotypic heterogeneity.
    J Exp Med. 1988 Nov 1;168(5):1607-20 PMID: 3141553
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1991-01-01
Pages
197-207
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118744
Subset
IM
Grants
NCI NIH HHS · CA-33399 · United States
NCI NIH HHS · CA-34233 · United States
NCI NIH HHS · K08 CA01396 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]