Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Myeloma and Plasma Cell Disorders

Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization

Leukemia volume 15, pages 840–845 (2001)Cite this article

Abstract

To analyze the genomic differences between multiple myeloma (MM) and plasma cell leukemia (PCL), a total of 30 cases were studied by comparative genomic hybridization (CGH). In five cases with a low proportion of plasma cells (PC) in bone marrow, an enrichment of PC was performed by using immunomagnetic beads conjugated with the monoclonal antibody B-B4. In 24 out of the 25 MM (96%) and in all five PCL (100%) patients DNA copy number changes were identified by CGH analysis; in the MM case without chromosomal imbalances, the immunomagnetic enrichment of PC had failed. The most recurrent changes in MM patients were gains at chromosomes 15q (48%), 11q (44%), 3q (40%), 9q (40%) and 1q (36%). By contrast, all PCL patients showed gains in 1q. Losses of chromosomal material were significantly more frequent in PCL than in MM patients (P = 0.03): losses on 13q in 80% of PCL vs 28% of MM; and on chromosome 16 in 80% vs 12%, respectively. In addition, PCL patients showed losses of 2q and 6p that were not present in MM. The CGH data show differences in chromosomal imbalances between MM and PCL.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Zandecki M, Lai JL, Facon T . Multiple myeloma: almost all patients are cytogenetically abnormal Br J Haematol 1996 94: 217–227

    Article  CAS  PubMed  Google Scholar 

  2. Brigaudeau C, Trimoreau F, Gachard N, Rouzier E, Jaccard A, Bordessoule D, Praloran V . Cytogenetic study of 30 patients with multiple myeloma: comparison of 3 and 6 day bone marrow cultures stimulated or not with cytokines by using a miniaturized karyotypic method Br J Haematol 1997 96: 594–600

    Article  CAS  PubMed  Google Scholar 

  3. Facon T, Lai JL, Nataf E, Preudhomme C, Zandecki M, Hammad M, Wattel E, Jouet JP, Bauters F . Improved cytogenetic analysis of bone marrow plasma cells after cytokine stimulation in multiple myeloma: a report on 46 patients Br J Haematol 1993 84: 743–745

    Article  CAS  PubMed  Google Scholar 

  4. Smadja NV, Louvet C, Isnard F, Dutel JL, Grange MJ, Varette C, Krulik M . Cytogenetic study in multiple myeloma at diagnosis: comparison of two techniques Br J Haematol 1995 90: 619–624

    Article  CAS  PubMed  Google Scholar 

  5. Hernández JM, Gutiérrez NC, Almeida J, García JL, Sánchez MA, Mateo G, Ríos A, San Miguel JF . IL-4 improves the detection of cytogenetic abnormalities in multiple myeloma and increases the proportion of clonally abnormal metaphases Br J Haematol 1998 103: 163–167

    Article  PubMed  Google Scholar 

  6. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D . Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors Science 1992 258: 818–821

    Article  CAS  PubMed  Google Scholar 

  7. Avet-Loiseau H, Andree-Ashley LE, Moore D, Mellerin MP, Feusner J, Bataille R, Pallavicini MG . Molecular cytogenetic abnormalities in multiple myeloma and plasma cell leukemia measured using comparative genomic hybridization Genes Chromos Cancer 1997 19: 124–133

    Article  CAS  PubMed  Google Scholar 

  8. Cigudosa JC, Rao PH, Calasanz MJ, Odero MD, Michaeli J, Jhanwar SC, Chaganti RS . Characterization of nonrandom chromosomal gains and losses in multiple myeloma by comparative genomic hybridization Blood 1998 91: 3007–3010

    CAS  PubMed  Google Scholar 

  9. Aalto Y, Nordling S, Kivioja AH, Karaharju E, Elomaa I, Knuutila S . Among numerous DNA copy number changes, losses of chromosome 13 are highly recurrent in plasmacytoma Genes Chromos Cancer 1999 25: 104–107

    Article  CAS  PubMed  Google Scholar 

  10. García-Sanz R, Orfao A, González M, Tabernero MD, Bladé J, Moro MJ, Fernández-Calvo J, Sanz MA, Pérez-Simón JA, Rasillo A, San Miguel JF . Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics Blood 1999 93: 1032–1037

    PubMed  Google Scholar 

  11. Dimopoulos MA, Palumbo A, Delasalle KB, Alexanian R . Primary plasma cell leukaemia Br J Haematol 1994 88: 754–759

    Article  CAS  PubMed  Google Scholar 

  12. Chronic Leukemia-Myeloma Task Force NCI . Proposed guidelines for protocol studies: plasma cell myeloma Cancer Chemother Rep 1973 4: 145–158

    Google Scholar 

  13. Durie BGM, Salmon SE . A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival Cancer 1975 36: 842–854

    Article  CAS  PubMed  Google Scholar 

  14. Avet-Loiseau H, Li JY, Facon T, Brigaudeau C, Morineau N, Maloisel F, Rapp MJ, Talmant P, Trimoreau F, Jaccard A, Harousseau JL, Bataille R . High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies Cancer Res 1998 58: 5640–5645

    CAS  PubMed  Google Scholar 

  15. ISCN . Guidelines for Cancer Cytogenetics. Supplement to: An International System for Human Cytogenetic Nomenclature Karger: Basel 1995

    Google Scholar 

  16. Sambrook J, Fritsch EF, Maniatis T . Molecular Cloning: A Laboratory Manual Cold Spring Harbor Laboratory Press: Cold Spring Harbor 1989

    Google Scholar 

  17. Lichter P, Bentz M, du Manoir S, Joos S . Comparative genomic hybridization. In: Vernon RS, Babu A (eds) Human Chromosomes. Principles and Techniques McGraw-Hill: New York 1995 pp 191–210

    Google Scholar 

  18. Beá S, Ribas M, Hernández JM, Bosch F, Pinyol M, Hernández L, García JL, Flores T, González M, López-Guillermo A, Piris MA, Cardesa A, Montserrat E, Miró R, Campo E . Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants Blood 1999 93: 4365–4374

    PubMed  Google Scholar 

  19. Monni O, Oinonen R, Elonen E, Franssila K, Teerenhovi L, Joensuu H, Knuutila S . Gain of 3q and deletion of 11q22 are frequent aberrations in mantle cell lymphoma Genes Chromos Cancer 1998 21: 298–307

    Article  CAS  PubMed  Google Scholar 

  20. Knuutila S, Autio K, Aalto Y . Online access to CGH data of DNA sequence copy number changes Am J Pathol 2000 157: 689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ried T, Heselmeyer-Haddad K, Blegen H, Schrock E, Auer G . Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation Genes Chromos Cancer 1999 25: 195–204

    Article  CAS  PubMed  Google Scholar 

  22. Brito-Babapulle V, Atkin NB . Break points in chromosome 1 abnormalities of 218 human neoplasms Cancer Genet Cytogenet 1981 4: 215–222

    Article  CAS  PubMed  Google Scholar 

  23. Johansson B, Mertens F, Mitelman F . Cytogenetic evolution patterns in non-Hodgkin's lymphoma Blood 1995 86: 3905–3914

    CAS  PubMed  Google Scholar 

  24. Sawyer JR, Tricot G, Mattox S, Jagannath S, Barlogie B . Jumping translocations of chromosome 1q in multiple myeloma: evidence for a mechanism involving decondensation of pericentromeric heterochromatin Blood 1998 91: 1732–1741

    CAS  PubMed  Google Scholar 

  25. Calasanz MJ, Cigudosa JC, Odero MD, Ferreira C, Ardanaz MT, Fraile A, Carrasco JL, Solé F, Cuesta B, Gullón A . Cytogenetic analysis of 280 patients with multiple myeloma and related disorders: primary breakpoints and clinical correlations Genes Chromos Cancer 1997 18: 84–93

    Article  CAS  PubMed  Google Scholar 

  26. Rao PH, Cigudosa JC, Ning Y, Calasanz MJ, Iida S, Tagawa S, Michaeli J, Klein B, Dalla-Favera R, Jhanwar SC, Ried T, Chaganti RS . Multicolor spectral karyotyping identifies new recurring breakpoints and translocations in multiple myeloma Blood 1998 92: 1743–1748

    CAS  PubMed  Google Scholar 

  27. Sawyer JR, Lukacs JL, Munshi N, Desikan KR, Singhal S, Mehta J, Siegel D, Shaughnessy J, Barlogie B . Identification of new nonrandom translocations in multiple myeloma with multicolor spectral karyotyping Blood 1998 92: 4269–4278

    CAS  PubMed  Google Scholar 

  28. Chang H, Bouman D, Boerkoel CF, Stewart AK, Squire JA . Frequent monoallelic loss of D13S319 in multiple myeloma patients shown by interphase fluorescence in situ hybridization Leukemia 1999 13: 105–109

    Article  CAS  PubMed  Google Scholar 

  29. Dao DD, Sawyer JR, Epstein J, Hoover RG, Barlogie B, Tricot G . Deletion of the retinoblastoma gene in multiple myeloma Leukemia 1994 8: 1280–1285

    CAS  PubMed  Google Scholar 

  30. Pérez-Simón JA, García-Sanz R, Tabernero MD, Almeida J, González M, Fernández-Calvo J, Moro MJ, Hernández JM, San Miguel JF, Orfao A . Prognostic value of numerical chromosome aberrations in multiple myeloma: a FISH analysis of 15 different chromosomes Blood 1998 91: 3366–3371

    PubMed  Google Scholar 

  31. Tricot G, Sawyer JR, Jagannath S, Desikan KR, Siegel D, Naucke S, Mattox S, Bracy D, Munshi N, Barlogie B . Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants J Clin Oncol 1997 15: 2659–2666

    Article  CAS  PubMed  Google Scholar 

  32. Bentz M, Dohner H, Huck K, Schutz B, Ganser A, Joos S, du Manoir S, Lichter P . Comparative genomic hybridization in the investigation of myeloid leukemias Genes Chromos Cancer 1995 12: 193–200

    Article  CAS  PubMed  Google Scholar 

  33. Persson K, Pandis N, Mertens F, Borg A, Baldetorp B, Killander D, Isola J . Chromosomal aberrations in breast cancer: a comparison between cytogenetics and comparative genomic hybridization Genes Chromos Cancer 1999 25: 115–122

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partially supported by grants from the Spanish FIS (97/1248; 98/1161 and 00/1089). The authors thank ME Fernández, P Fernández, MA Hernández and M Anderson for technical assistance.

Author information

Authors and Affiliations

  1. Servicio de Hematología, Hospital Universitario de Salamanca and Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Spain

    NC Gutiérrez, JM Hernández, JL García, MC Cañizo, M González, MB González, MA García-Marcos & JF San Miguel

  2. Hospital General de Segovia, Spain

    J Hernández

Authors
  1. NC Gutiérrez
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. JM Hernández
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. JL García
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. MC Cañizo
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. M González
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. J Hernández
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. MB González
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. MA García-Marcos
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. JF San Miguel
    View author publications

    You can also search for this author inPubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gutiérrez, N., Hernández, J., García, J. et al. Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization. Leukemia 15, 840–845 (2001). https://doi.org/10.1038/sj.leu.2402116

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402116

Keywords

This article is cited by

Search

Advanced search

Quick links