Detection of Residual Leukemic Cells in Adult Acute Lymphoblastic Leukemia by Analysis of Gene Rearrangements and Correlation with Early Relapses

  • W. U. Knauf
  • A. D. Ho
  • D. Hoelzer
  • E. Thiel
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 131)

Abstract

Improvements in complete remission (CR) rate and long-term survival in adult acute lymphoblastic leukemia (ALL) have been achieved during the past decade by intensive chemotherapy. Today, more than 75% of the patients attain a CR (Hoelzer et al. 1984; Clarkson et al. 1985; Jacobs and Gale 1984). Nevertheless, the recurrence rate remains high. Only about 40% of patients are still alive and in CR after 5 years (Hoelzer et al. 1984; Clarkson et al. 1985; Jacobs and Gale 1984). Half of the relapses occur within the first year after the diagnosis has been established. Using multivariate analysis, patients can be categorized to be at high risk for relapse according the following criteria: high initial cell count, age over 35 years, null cell ALL immunophenotype, no CR after 4 weeks’ induction therapy (Hoelzer et al. 1984). Recurrent disease is probably due to residual leukemic cells. Gene rearrangements are used as markers of clonality and thereby monoclonal lymphoid cells can be detected with an high degree of sensitivity (Korsmeyer et al. 1983; Aisenberg and Wilkes 1985; Raghavachar et al. 1986). Even in bone marrow samples considered morphologically to be free from leukemic cells, analysis of gene rearrangements is still able to give evidence of persisting disease (Zehnbauer et al. 1986). In this study, we have applied the analysis of gene rearrangements to detect residual disease in patients considered to be in CR after a standardized induction therapy. The laboratory findings were correlated with the duration of clinical remission and the relapse rate. The aim of the study was to assess the influence of residual disease on the rate of early relapses in ALL.

Keywords

Lymphoma EDTA Leukemia Agarose Electrophoresis 

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References

  1. Alsenberg AC, Wilkes BM (1985) The phenotype and genotype of T-cell and Non-T, Non-B acute lymphoblastic leukemia. Blood 66: 1215–1218Google Scholar
  2. Aisenberg AC, Krontiris TG, Mak TW, Wilkes BM (1985) Rearrangement of the gene for the beta chain of the T-cell receptor in T-cell chronic lymphocytic leukemia and related disorders. N Engl J Med 313: 538–542CrossRefGoogle Scholar
  3. Arnold A, Cossman J, Bakhshi A, Jaffe ES, Waldmann TA, Korsmeyer SJ (1983) Immunoglobulin gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med 309: 1593–1599PubMedCrossRefGoogle Scholar
  4. Bird J, Galili N, Link M, Stites D, Sklar J (1988) Continuing rearrangement but absence of somatic hypermutation in immunoglobulin genes of human B cell precursor leukemia. J Exp Med 168: 229–245PubMedCrossRefGoogle Scholar
  5. Bregni M, Siena S, Neri A, Bassan R, Barbui T, Delia D, Bonnadonna G, DallaFavera R, Gianni AM (1989) Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis. J Clin Oncol 7: 338–343PubMedGoogle Scholar
  6. Clarkson B, Ellis S, Little C, Gee T, Arlin Z, Mertelsmann R, Andreef M, Kempin A, Koziner B, Chaganti R, Jhanwar S, McKenzie S, Cirrincione C, Gaynor J (1985) Acute lymphoblastic leukemia in adults. Semin Oncol 12: 160–179PubMedGoogle Scholar
  7. Cleary ML, Chao J, Warnke R, Sklar J (1984) Immunoglobulin gene rearrangement as diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci USA 81: 539–597CrossRefGoogle Scholar
  8. Deane M, Norton JD (1991) Immunoglobulin gene “fingerprinting”: an approach to analysis of B lymphoid clonality in lymphoproliferative disorders. Br J Haematol 77: 274–281PubMedCrossRefGoogle Scholar
  9. Estrov Z, Grunberger T, Dube ID, Wang YP, Freedman MH (1986) Detection of residual acute lymphoblastic leukemia cells in cultures of bone marrow obtained during remission. N Engl J Med 315: 538–542PubMedCrossRefGoogle Scholar
  10. Hansen-Hagge TE, Yokota S, Bartram CR (1989) Detection of minimal residual disease in acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain sequences. Blood 74: 1762–1767PubMedGoogle Scholar
  11. Hoelzer D, Thiel E, Löffler H, Bodenstein H, Plaumann L, Büchner T, Urbanitz D, Koch P, Heimpel H, Engelhardt R, Müller U, Wendt EC, Sodomann H, Rühl H, Herrmann F, Kaboth W, Dietzfelbinger H, Pralle H, Lunscken C, Hellriegel KP, Spors S, Nowrousian RM, Fischer J, Fülle H, Mitrou PS, Pfreundschuh M, Görg C, Emmerich B, Queisser W, Meyer P, Labedzki L, Essers U, König H, Mainzer K, Herrmann R, Messerer D, Zwingers T (1984) Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. Blood 64: 38–47PubMedGoogle Scholar
  12. Hu E, Thompson J, Horning S, Trela M, Lowder J, Levy R, Sklar J (1985) Detection of B-cell lymphoma in peripheral blood by DNA hybridization. Lancet 11: 1092–1095CrossRefGoogle Scholar
  13. Jacobs AD, Gale RP (1984) Recent advances in the biology and treatment of acute lymphoblastic leukemia in adults. N Engl J Med 311: 1219–1231PubMedCrossRefGoogle Scholar
  14. Korsmeyer SJ, Arnold A, Bakhshi A, Ravetch JV, Siebenlist U, Hieter PA, Sharrow SO, LeBien TW, Kersey JH, Poplack DG, Leder P, Waldmann TA (1983) Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins. J Clin Invest 71: 301–313PubMedCrossRefGoogle Scholar
  15. Lee MS, Chang KS, Cabanillas F, Freireich EJ, Trujillo JM, Stass SA (1987) Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification. Science 237: 175–178PubMedCrossRefGoogle Scholar
  16. Lee MS, Chang KS, Freireich EJ, Kantarijan HM, Talpaz M, Trujillo JM, Stass SA (1988) Detection of minimal residual bcr/abl transcripts by a modified polymerase chain reaction. Blood 72: 893–897PubMedGoogle Scholar
  17. Minden MD, Mak TW (1986) The structure of the T cell antigen receptor in normal and malignant T cells. Blood 68: 327–336PubMedGoogle Scholar
  18. Raghavachar A, Bartram CR, Ganser A, Heil G, Kleihauer E, Kubanek B (1986) Acute undifferentiated leukemia: Implications for cellular origin and clonality suggested by analysis of surface markers and immunoglobulin gene rearrangement. Blood 68: 658–662PubMedGoogle Scholar
  19. Ravetch JV, Siebenlist U, Korsmeyer SJ, Waldmann T, Leder P (1981) The structure of the immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes. Cell 27: 583–591Google Scholar
  20. Rigby DJ, Dieckman M, Rhodes C, Berg P (1977) Labeling deoxyribonucleic acid to high specific activity in-vitro by nick translation with DNA polymerase I. J Mol Biol 113: 237–251PubMedCrossRefGoogle Scholar
  21. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 1860–1861CrossRefGoogle Scholar
  22. Wright PP, Poplack DG, Bakhshi A, Reaman DG, Cole D, Jensen JP, Korsmeyer SJ (1987) Gene rearrangements as markers of clonal variation and minimal residual disease in acute lymphoblastic leukemia. J Clin Oncol 5: 735–741PubMedGoogle Scholar
  23. Yanagi Y, Yoshikai Y, Legget K, Clark SP, Aleksander I, Mak TW (1984) A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308: 145–149PubMedCrossRefGoogle Scholar
  24. Zehnbauer BA, Pardoll DM, Burke PJ, Graham ML, Vogelstein B (1986) Immunoglobulin gene rearrangements in remission bone marrow specimens from patients with acute lymphoblastic leukemia. Blood 67: 835–838PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1993

Authors and Affiliations

  • W. U. Knauf
    • 1
  • A. D. Ho
    • 2
  • D. Hoelzer
    • 3
  • E. Thiel
    • 1
  1. 1.Department of Hematology, Klinikum SteglitzFree University of BerlinBerlin 45Fed. Rep. of Germany
  2. 2.Northeastern Ontario Oncology ProgrammeSudburyCanada
  3. 3.Department of HematologyUniversity of FrankfurtFrankfurtFed. Rep. of Germany

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