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:

Therapy and Follow up Studies

Use of dual-color interphase FISH for the detection of inv(16) in acute myeloid leukemia at diagnosis, relapse and during follow-up: a study of 23 patients

Leukemia volume 14, pages 364–368 (2000)Cite this article

Abstract

The value of dual-color fluorescence in situ hybridization (FISH) for the detection of inv(16), using two contigs of cosmid probes mapping on both sides of the chromosome 16p breakpoint region, was evaluated in 23 acute myeloid leukemias (AML) in different phases of the disease. At diagnosis interphase FISH detected inv(16) in 19/19 (100%) cases with conventional cytogenetics (CC) evident aberration and excluded the rearrangement in two patients with CC suspected inv(16). Moreover, it also identified an associated del(16p) in two patients. At relapse, it revealed the inv(16) in 8/8 (100%) studied cases. These results were concordant with those of reverse transcriptase-polymerase chain reaction (RT-PCR). From 13 patients who obtained at least one complete remission (CR), 31 follow-up samples were analyzed using interphase FISH. Twenty-nine specimens scored negative for inv(16) and two were positive. RT-PCR detected CBFβ/MYH11 transcripts in four of the nine CR samples analyzed, being more sensitive than interphase FISH. Eight of the 13 patients relapsed at a median time of 6.5 months (range 1–15) from the last negative FISH analysis. Of the two patients with positive FISH in CR, one relapsed soon after. At diagnosis and relapse, interphase-FISH proved to be an effective technique for detecting inv(16) appearing more sensitive than CC. Prospective studies with more frequent controls and possibly additional FISH probes are needed to assess the value of interphase FISH for minimal residual disease (MRD) and relapse prediction.

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

Access options

Buy this article

  • Purchase on Springer Link
  • 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. Le Beau MM, Larson RA, Bitter MA, Vardiman JW, Golomb HM, Rowley JD . Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia New Engl J Med 1983 309: 630–636

    Article  CAS  Google Scholar 

  2. Rowley JD . Recurring chromosome abnormalities in leukemia and lymphoma Semin Hematol 1990 27: 122–136

    CAS  PubMed  Google Scholar 

  3. Liu PP, Hajra A, Wijmenga C, Collins FS . Molecular pathogenesis of the chromosome 16 inversion in the M4Eo subtype of acute myeloid leukemia Blood 1995 85: 2289–2302

    CAS  PubMed  Google Scholar 

  4. van der Reijden BA, Lombardo M, Dauwerse HG, Giles RH, Mühlematter D, Jotterand Bellomo M, Wessels HW, Beverstock GC, van Ommen GJB, Hagemeijer A, Breuning MH . RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of a new alternative splicing in CBFβ-MYH11 transcripts Blood 1995 86: 277–282

    CAS  PubMed  Google Scholar 

  5. Mrozek K, Heinonen K, de la Chapelle, Bloomfield CD . Clinical significance of cytogenetics in acute myeloid leukemia Semin Oncol 1997 24: 17–31

    CAS  PubMed  Google Scholar 

  6. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A . The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 Trial Blood 1998 92: 2322–2333

    CAS  PubMed  Google Scholar 

  7. Liu P, Tarlè SA, Hajra A, Claxton DF, Marlton P, Freedman M, Siciliano MJ, Collins FS . Fusion between trancription factor CBFb/PEBP2b and a myosin heavy chain in acute myeloid leukemia Science 1993 261: 1041–1044

    Article  CAS  Google Scholar 

  8. Dauwerse JG, Wessels JW, Giles RH, Wiegant J, Raap AK, van der Reijden BA, Fugazza G, Jumelet EA, Smit E, Baas F, Hagemeijer A, Beverstock GC, van Ommen GJB, Breuning MH . Cloning the breakpoint cluster region of the inv(16) in acute nonlymphocytic leukemia M4 Eo Hum Mol Genet 1993 2: 1527–1534

    Article  CAS  Google Scholar 

  9. Kuss BJ, Deeley RG, Cole SPG, Willman CL, Kopecky KJ, Wolman SR, Eyre HJ, Lane SA, Nancarrow JK, Withmore SA, Callen DF . Deletion of gene for multidrug resistance in acute myeloid leukemia with inversion in chromosome 16: prognostic implications Lancet 1994 343: 1531–1534

    Article  CAS  Google Scholar 

  10. Martinet D, Mühlematter D, Leeman M, Parlier V, Hess U, Gmür J Jotterand M . Detection of 16p deletions by FISH in patients with inv(16) or t(16;16) and myeloid leukemia (AML) Leukemia 1997 11: 964–970

    Article  CAS  Google Scholar 

  11. Claxton DF, Liu P, Hsu HB, Marlton P, Hester J, Collins F, Deisseroth AB, Rowley JD, Siciliano MJ . Detection of fusion transcripts generated by the inversion 16 chromosome in acute myelogenous leukemia Blood 1994 83: 1750–1756

    CAS  PubMed  Google Scholar 

  12. Hebert J, Cayuela J-M, Daniel M-T, Berger R, Sigaux F . Detection of minimal residual disease in acute myelomonocytic leukemia with abnormal marrow eosinophils by nested polymerase chain reaction with allele specific amplification Blood 1994 84: 2291–2296

    CAS  PubMed  Google Scholar 

  13. Sacchi N, Magnani I, Kearney L, Wijsman J, Hagemeijer A, Darfler M . Interphase cytogenetics of the t(8;21)(q22;q22) associated with acute myelogenous leukemia by two colour fluorescence in situ hybridization Cancer Genet Cytogenet 1995 79: 97–103

    Article  CAS  Google Scholar 

  14. Mancini M, Nanni M, Cedrone M, Diverio D, Avvisati G, Riccioni R, De Cuia MR, Fenu S, Alimena G . Combined cytogenetic, FISH and molecular analysis in acute promyelocytic leukemia at diagnosis and in complete remission Br J Haematol 1995 91: 878–884

    Article  CAS  Google Scholar 

  15. Liu P, Claxton DF, Marlton P, Hajra A, Siciliano J, Freedman M, Chandrasekharappa SC, Yanagisawa K, Stallings RL, Collins FS, Siciliano MJ . Identification of yeast artificial chromosomes containing the inversion 16 p-arm breakpoint associated with acute myelomonocytic leukemia Blood 1993 82: 716–721

    CAS  PubMed  Google Scholar 

  16. Dauwerse JG, Kievits T, Beverstock GC, van der Keur D, Smit E, Wessels HW, Hagemeijer A, Pearson PL, Van Ommen G-JB, Breuning MH . Rapid detection of chromosome 16 inversion in acute nonlymphocytic leukemia, subtype M4, regional localization of the breakpoint in 16p Cytogenet Cell Genet 1990 53: 126–128

    Article  CAS  Google Scholar 

  17. ISCN. An International System for Human Cytogenetic Nomenclature. Mitelman F (ed) S Karger: Basel, 1995

  18. Arnoldus EPJ, Wiegant J, Noordmeer IA, Wessels JW, Beverstock GC, Grosveld GC, van der Ploeg M, Raap AK . Detection of Philadelphia chromosome in interphase nuclei Cytogenet Cell Genet 1990 54: 108–111

    Article  CAS  Google Scholar 

  19. Chomczynsky P, Sacchi N . Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Anal Biochem 1987 162: 156–160

    Google Scholar 

  20. Dierlamm J, Stul M, Vranckx H, Michaux L, Olde Weghuis DEM, Speleman F, Selleslag D, Kramer MHH, Noens L, Cassiman JJ, Van den Berghe H, Hagemeijer A . FISH identifies inv(16)(p13q22) masked by translocations in three cases of acute myeloid leukemia Genes Chromosom Cancer 1998 22: 87–94

    Article  CAS  Google Scholar 

  21. Vandenberghe P, Verhoef GEG, Emonds MP, Demuynck H, Zachée P, De Wolf-Peeters C, Decorte R, Cassiman JJ, Boogaerts MA . A single course of remission reinduction chemotherapy for acute myelogenous leukemia relapsing after allogeneic bone marrow transplantation is complicated by graft-versus-host disease and followed by sustained complete remission Leukemia 1997 11: 1775–1778

    Article  CAS  Google Scholar 

  22. Dauwerse HG, Smit EME, Giles RH, Slater R, Breuning MH, Hagemeijer A, van der Reijden BA . Two-colour FISH detection of the inv(16) in interphase nuclei of patients with acute myeloid leukemia Br J Haematol 1999 106: 111–114

    Article  CAS  Google Scholar 

  23. Nucifora G, Larson RA, Rowley JD . Persistence of the 8;21 translocation in patients with acute myeloid leukemia type M2 in long-term remission Blood 1993 82: 712–715

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Biomed Concerted Action: contract grant CT 94-1703; the Belgian programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming (the scientific responsibility is assumed by the authors); the Flemish Government in the frame of the action Kom op tegen Kanker/Vlaamse Kankerliga and partially by MURST fondi 60% (GA). We gratefully acknowledge the collaboration of Dr A Bosly, P Brock, A Ferrant, D Selleslag and G Verhoef, for providing the clinical data and of Dr B Santulli for providing cytogenetic data of patient No. 23. C Mecucci is partially supported by AIRC.

Author information

Authors and Affiliations

  1. Department of Cellular Biotechnology and Hematology, University ‘La Sapienza’, Rome, Italy

    M Mancini, M Cedrone, D Diverio, M Brama, MR De Cuia, M Nanni, F Fazi & G Alimena

  2. Center for Human Genetics, University of Leuven, Leuven, Belgium

    B Emanuel, M Stul, H Vranckx & A Hagemeijer

  3. Hematology and Bone Marrow Transplantation Unit, University of Perugia, Italy

    C Mecucci

Authors
  1. M Mancini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Cedrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Diverio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Emanuel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Stul
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Vranckx
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Brama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. MR De Cuia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Nanni
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F Fazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Mecucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. G Alimena
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A Hagemeijer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mancini, M., Cedrone, M., Diverio, D. et al. Use of dual-color interphase FISH for the detection of inv(16) in acute myeloid leukemia at diagnosis, relapse and during follow-up: a study of 23 patients. Leukemia 14, 364–368 (2000). https://doi.org/10.1038/sj.leu.2401678

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2401678

Keywords

This article is cited by

Search

Advanced search

Quick links