No VH Somatic Hypermutation Was Detected in B-Cells of a Patient with Macroglobulinemia Due to Splenic Marginal Zone Lymphoma

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

B-cell diseases are classified on the basis of the normal differentiation stages. We report here a case of a patient with a long history of leukocytosis, splenomegaly without lymphadenopathy, and hyperviscosity symptoms. Clinically, the patient’s diagnosis was leukemic Waldenström macroglobulinemia. Chromosomal analysis revealed translocation t(2;7)(p11;q22) along with disease progression. Death occurred from pulmonary infection at 46 months after the initial presentation. At autopsy, malignant lymphocytes were found in the marginal areas of the spleen with spreading to the bone marrow and the liver. The histologic findings were consistent with splenic marginal zone lymphoma. We examined the sequences of the immunoglobulin VH gene in cells from the initial peripheral blood and from the spleen at autopsy and found that the sequences were identical and had no somatic hypermutation. Macroglobulinemia can occur in various B-cell disorders, including splenic marginal zone lymphoma, even with the transformation of unmutated B-lymphocytes. Int J Hematol. 2002;76:453-459.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Krueppers R, Klein U, Hansmann ML, Rajewsky K. Cellular origin of human B-cell lymphomas.N Engl J Med. 1999;341:1520–1529.

    Article  Google Scholar 

  2. 2.

    Harris NL, Jaffe ES, Stein H, et al. A revised European-Amerian classification of lymphoid neoplasms: a proposal from the international lymphoma study group.Blood. 1994;84:1361–1392.

    PubMed  PubMed Central  CAS  Google Scholar 

  3. 3.

    Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting—Airlie House,Virginia, November 1997.J Clin Oncol. 1999;17: 3835–3849.

    Article  PubMed  CAS  Google Scholar 

  4. 4.

    Krueppers R, Hansmann ML, Rajewsky K. Micromanipulation and PCR analysis of single cells from tissue sections. In: Weir DM, Blackwell C, Herzenberg LA, eds.Handbook of Experimental Immunology. 5th ed. New York, NY: Blackwell Scientific; 1996: 206.1–206.4.

    Google Scholar 

  5. 5.

    Ivanovski M, Silvestri F, Pozzato G, et al. Somatic hypermutation, clonal diversity, and preferential expression of the VH51p1/ VLkv325 immunoglobulin gene combination in hepatitis C virus-associated immunocytomas.Blood. 1998;91:2433–2442.

    PubMed  CAS  Google Scholar 

  6. 6.

    Cook GP, Tomlinson IM. The human immunoglobulin VH repertoire.Immunol Today. 1995;16:237–242.

    Article  PubMed  CAS  Google Scholar 

  7. 7.

    Van Huyen JPD, Molina T, Delmer A, et al. Splenic marginal zone lymphoma with or without plasmacytic differentiation.Am J Surg Pathol. 2000;24:1581–1592.

    Article  Google Scholar 

  8. 8.

    Tierens A, Delabie J, Pittaluga S, Driessen A, De Wolf-Peeters C. Mutation analysis of the rearranged immunoglobulin heavy chain genes of marginal zone cell lymphomas indicates an origin from different marginal zone B lymphocyte subsets.Blood. 1998;91: 2381–2386.

    PubMed  CAS  Google Scholar 

  9. 9.

    Zhu D, Oscier DG, Stevenson FK. Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes.Blood. 1995;85:1603–1607.

    PubMed  CAS  Google Scholar 

  10. 10.

    Miranda RN, Cousar JB, Hammer RD, Collins RD, Vnencak-Jones CL. Somatic mutation analysis of IgH variable regions reveals that tumor cells of most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zone B-cell lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes.Hum Pathol. 1999;30:306–312.

    Article  PubMed  CAS  Google Scholar 

  11. 11.

    Algara P, Mateo MS, Sanchez-Beato M, et al. Analysis of the IgVH somatic mutations in splenic marginal zone lymphomas defines a group of unmutated cases with frequent 7q deletion and adverse clinical course.Blood. 2002;99:1299–1304.

    Article  PubMed  CAS  Google Scholar 

  12. 12.

    Aoki H, Takishita M, Kosaka M, Saito S. Frequent somatic mutations in D and/or JH segments of Ig gene in Waldenström’s macroglobulinemia and chronic lymphocytic leukemia (CLL) with Richter’s syndrome but not in common CLL.Blood. 1995;85: 1913–1919.

    PubMed  CAS  Google Scholar 

  13. 13.

    Wagner SD, Martinelli V, Luzzatto L. Similar patterns of V k gene usage but different degrees of somatic mutations in hairy cell leukemia, prolymphocytic leukemia, Waldenström’s macroglobulinemia, and myeloma.Blood. 1994;83:3647–3653.

    PubMed  CAS  Google Scholar 

  14. 14.

    Hamblin T, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia.Blood. 1999;94: 1848–1854.

    PubMed  CAS  Google Scholar 

  15. 15.

    Corcoran MM, Mould SJ, Orchard JA, et al. Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations.Oncogene. 1999;18: 6271–6277.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Tetsuaki Sekikawa or Shinobu Takahara or Takeshi Kawano or Shuji Nakada or Kiyoshi Ito or Satsuki Iwase or Hisashi Yamada or Masayuki Kobayashi or Junko Horiguchi-Yamada.

About this article

Cite this article

Sekikawa, T., Takahara, S., Kawano, T. et al. No VH Somatic Hypermutation Was Detected in B-Cells of a Patient with Macroglobulinemia Due to Splenic Marginal Zone Lymphoma. Int J Hematol 76, 453–459 (2002). https://doi.org/10.1007/BF02982811

Download citation

Key words

  • SMZL
  • WM
  • Macroglobulinemia
  • Somatic hypermutation
  • Naive B-cell