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:

Cytogenetics

Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?

Abstract

We determined bone marrow karyotype at diagnosis in four female acute myeloid leukemia (AML) or myelodysplasia patients, aged between 52 and 56 years. In each case, we observed chromosome rearrangement involving the same 4q24 band. Three patients had a balanced reciprocal translocation as the sole abnormality – t(3;4)(q26;q24), t(4;5)(q24;p16) and t(4;7)(q24;q21) – and the fourth had del(4)(q23q24), +4. We used a set of 4q BAC probes for fluorescent in situ hybridization (FISH) in these four cases. We found a 4q24 submicroscopic deletion in all three translocations, with a common deletion of approximately 0.5 Mb. In three cases, we concluded that rearrangement occurred in an early hematopoietic stem cell, as it was detected, in mosaic with a normal karyotype, in a fraction of remission bone marrow cells, peripheral T and B lymphocytes, malignant lymph node T-lymphoma cells in one case and B-lymphoblastoid cell lines established in two cases. Moreover, one of 10 additional AML patients tested by FISH had a normal karyotype and deletion of one of the commonly deleted probe sequences. A tumor suppressor gene may therefore be involved, especially as two patients developed malignant lymphoma at the same time as myeloid proliferation.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Mitelman F, Johansson B, Mertens F . Mitelman database of chromosome aberrations in cancer 2001. http://cgap.nci.nih.gov/Chromosomes/Mitelman.

  2. Mrozek K, Heerema NA, Bloomfield CD . Cytogenetics in acute leukemia. Blood Rev 2004; 18: 115–136.

    Article  Google Scholar 

  3. Nilsson L, Astrand-Grundstrom I, Anderson K, Arvidsson I, Hokland P, Bryder D et al. Involvement and functional impairment of the CD34(+)CD38(−)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 2002; 100: 259–267.

    CAS  PubMed  Google Scholar 

  4. Fialkow PJ, Singer JW, Adamson JW, Vaidya K, Dow LW, Ochs J et al. Acute nonlymphocytic leukemia: heterogeneity of stem cell origin. Blood 1981; 57: 1068–1073.

    CAS  PubMed  Google Scholar 

  5. Ferraris AM, Broccia G, Meloni T, Canepa L, Sessarego M, Gaetani GF . Clonal origin of cells restricted to monocytic differentiation in acute nonlymphocytic leukemia. Blood 1984; 64: 817–820.

    CAS  PubMed  Google Scholar 

  6. Heaney ML, Golde DW . Myelodysplasia. N Engl J Med 1999; 340: 1649–1660.

    Article  CAS  Google Scholar 

  7. Janssen JW, Buschle M, Layton M, Drexler HG, Lyons J, van den Berghe H et al. Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin. Blood 1989; 73: 248–254.

    CAS  PubMed  Google Scholar 

  8. Tsukamoto N, Morita K, Maehara T, Okamoto K, Karasawa M, Omine M et al. Clonality in myelodysplastic syndromes: demonstration of pluripotent stem cell origin using X-linked restriction fragment length polymorphisms. Br J Haematol 1993; 83: 589–594.

    Article  CAS  Google Scholar 

  9. Haase D, Feuring-Buske M, Konemann S, Fonatsch C, Troff C, Verbeek W et al. Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations. Blood 1995; 86: 2906–2912.

    CAS  PubMed  Google Scholar 

  10. Miyamoto T, Weissman IL, Akashi K . AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukaemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 2000; 97: 7521–7526.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  12. Maserati E, Aprilui F, Vinante F, Locatelli F, Amendola G, Zatterale A et al. Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15–20% of cases. Genes Chromosomes Cancer 2002; 33: 93–97.

    Article  CAS  Google Scholar 

  13. Bodmer D, Eleveld M, Kater-Baats E, Janssen I, Janssen B, Weterman M et al. Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21). Hum Mol Genet 2002; 11: 641–649.

    Article  CAS  Google Scholar 

  14. Yeo W, Wong N, Chow J, Tsoi WC, Johnson PJ, Wickham N . Small cell variant of Ki-1 lymphoma associated with myelofibrosis and a novel constitutional chromosomal translocation t(3;4) (q13;q12). J Clin Pathol 1996; 49: 259–262.

    Article  CAS  Google Scholar 

  15. Daibata M, Nemoto Y, Komatsu N, Machida H, Miyoshi I, Taguchi H . Constitutional t(3;11)(p21;q23) in a family, including one member with lymphoma: establishment of novel cell lines with this translocation. Cancer Genet Cytogenet 2000; 117: 28–31.

    Article  CAS  Google Scholar 

  16. Kitamura E, Kuemerle BA, Chernova OB, Cowell JK . Molecular characterization of the breakpoint region associated with a constitutional t(2;15)(q34;q26) in a patient with multiple myeloma. Cancer Genet Cytogenet 2001; 129: 112–119.

    Article  CAS  Google Scholar 

  17. Lafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y et al. Detection of large-scale variation in the human genome. Nat Genet 2004; 36: 949–951.

    Article  Google Scholar 

  18. Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P et al. Large-scale copy number polymorphism in the human genome. Science 2004; 305: 525–528.

    Article  CAS  Google Scholar 

  19. Huntly BJ, Bench A, Green AR . Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia. Blood 2003; 102: 1160–1168.

    Article  CAS  Google Scholar 

  20. Kolomietz E, Al-Maghrabi J, Brennan S, Karaskova J, Minkin S, Lipton J et al. Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis. Blood 2001; 97: 3581–3588.

    Article  CAS  Google Scholar 

  21. Christensen K, Kristiansen M, Hagen-Larsen H, Skytthe A, Bathum L, Jeune B et al. X-linked genetic factors regulate hematopoietic stem-cell kinetics in females. Blood 2000; 95: 2449–2451.

    CAS  PubMed  Google Scholar 

  22. Cools J, Stover EH, Wlodarska I, Marynen P, Gilliland DG . The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Curr Opin Hematol 2004; 11: 51–57.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M Rocchi and P de Jong for kindly supplying us with BAC probes. We also thank Cochin Hospital Cell Bank (Dr D Recan) for establishing lymphoblastoid cell lines and Fanny Couturier and Nathalie Koehler for excellent technical assistance. This study was supported in part by funds from the Comité de Paris de la Ligue Nationale Contre le Cancer.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F Viguié.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Viguié, F., Aboura, A., Bouscary, D. et al. Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?. Leukemia 19, 1411–1415 (2005). https://doi.org/10.1038/sj.leu.2403818

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403818

Keywords

This article is cited by

Search

Quick links