Genetic Relatedness of Lymphoid Malignancies: Transformation of Chronic Lymphocytic Leukemia as a Model

  1. Kenneth A. Foon, MD;
  2. Raghu Thiruvengadam, MD;
  3. Alan Saven, MD;
  4. Zale P. Bernstein, MD; and
  5. Robert Peter Gale, MD, PhD
  1. From the Markey Cancer Center and the Division of Hematology and Oncology, Department of Medicine, University of Kentucky, Lexington, Kentucky; Scripps Clinic and Research Foundation, La Jolla, California; Roswell Park Cancer Institute, Buffalo, New York; University of California at Los Angeles, Los Angeles, California. Requests for Reprints: Kenneth A. Foon, MD, Markey Cancer Center, 800 Rose Street, Room 140, Lexington, KY 40536-0093. Acknowledgments: The authors thank Drs. John Spinosa and Douglas Ellison for histopathologic materials, Dr. Richard McPherson for the Southern blot, and Dr. Ann Marie Block for the karyotype.

    Abstract

    Objective: Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that develop in about 10% of affected persons were reviewed. These B-cell cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. Two possible relations were evaluated: development from the chronic lymphocytic leukemia clone (clonal evolution) and development of a genetically unrelated, independent second cancer.

    Data Analysis: Analysis of genetic relatedness between the two cancers considered concordance for immunoglobulin gene rearrangements, for immunoglobulin isotypes and idiotypes, and for cytogenetic abnormalities.

    Conclusions: In the case of large B-cell lymphoma, generally thought to arise from the chronic lymphocytic leukemia clone, approximately one half of the patients had genetically unrelated cancers. In prolymphocytic transformation, all cases studied appeared to evolve from the chronic lymphocytic leukemia clone. The few studies of acute lymphoblastic leukemia and multiple myeloma showed genetic relatedness in some cases and unrelatedness in others. These data indicate that progression to more aggressive B-cell cancers in persons with chronic lymphocytic leukemia can result from either clonal evolution or from an independent transforming event.

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    1. Ann Intern Med July 1, 1993 vol. 119 no. 1 63-73
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