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.

  • Correspondence
  • Published:

Breakpoint analysis by fluorescence in situ hybridization in myelodysplastic syndromes with t(3;12)(q26;p13) and expression of EVI1

Leukemia volume 14, pages 1857–1858 (2000)Cite this article

Case 1: A 70-year-old male patient with an unremarkable medical history was admitted to the hospital with general malaise and an increased leucocyte count of 19.7 × 109/1 with a normal differential count. On examination no abnormalities were noted except for a mild splenomegaly. The haemoglobin concentration (Hb) was 12.7 g/dl (n: 14.0–17.1) with a platelet count of 450 × 109/1 (n: 150–350) with aggregates. The blood chemical findings were normal except for an increased level of lactate dehydrogenase of 415 U/l (n:114–235 U/l). A cytological bone marrow examination showed increased cellularity mainly due to increased myelopoiesis and megakaryopoiesis with only minor dysplastic features. Cytogenetic analysis showed a normal male karyotype. By multiplex and nested polymerase chain reaction (PCR) no bcr-abl fusion could be detected. A myeloproliferative syndrome without a specific classification was diagnosed. He was doing well for 2 years until a further increase in leucocyte count of 24.3 × 109/1 with 1.7 × 109/1 monocytes and a severe anemia (Hb 7.4 g/dl) developed with a platelet count of 212 × 109/1 and persistence of aggregation. By cytologic examination of the bone marrow an increase in cellularity was noted with 8% blasts and dysplastic features in all lineages with a prominent increase in megakaryocytes with apparent immature forms. In the peroxidase and Sudan Black staining 20% of the blasts stained positive with sporadic auer rods. Cytogenetic analysis showed a 46,XY,t(3;12)(q26;p13)[19]/46,XY[3]. A chronic myelomonocytic leukemia according to FAB classification (International Prognostic Score System: IPSS at diagnosis of 1.0; intermediate risk 1) with progression to RAEB-t with a unique t(3;12) was diagnosed. Hydroxyurea was started with only minor response. Splenectomy followed. He died of a cardiac event 18 months after the start of treatment.

Case 2: A 46-year-old woman with an unremarkable medical history was admitted to the hospital with bruising. On examination no abnormalities could be found except for some ecchymoses on her legs. Laboratory values revealed an Hb of 9.7 g/dl (n: 12.1–16.0), a leucocyte count of 4.5 × 109/1 with 35% granulocytes, 46% lymphocytes, 7% monocytes, 10% bands, 1% metamyelocytes and 1% blasts. The platelet count was 36 × 109/1 with several giant platelets. Blood chemical values were all normal. A cytological examination showed an increased cellularity with 23% blasts and strong dysplastic features most prominent in the myeloid lineage. Six percent of the blasts stained positive for peroxidase and Sudan Black. Cytogenetic analysis showed a 46,XX, t(3;12) (q2?5;p1?2)[20]. A diagnosis of RAEB-t (IPSS of 2.5; high risk) in progression to AML with an unique t(3;12) was diagnosed. She was treated with daunorubicin, cytosine arabinoside Ara-C and granulocyte–macrophage colony-stimulating factor (GM-CSF) according to an AML protocol without any response. She died 3 months after diagnosis.

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

References

  1. Baens M, Wlodarsky I, Corveleyn A, Hoornaert I, Hagemeijer A, Marynen P . A physical, transcript, and deletion map of chromosome region 12p12.3 flanked by ETV6 and CDKN1B: hypermethylation of the LRP6 CpC island in two leukemia patients with hemizygous del (12p) Genomics 1999 56: 40–50

    Article  CAS  Google Scholar 

  2. Brada S, De Wolf JThM, Hendriks D, Esselink M, Ruiters M, Vellenga E . The supportive effects of erythropoietin and mast cell growth factor on CD34+/CD36− sorted bone marrow cells of myelodysplasia patients Blood 1996 88: 505–510

    CAS  PubMed  Google Scholar 

  3. Raynaud SD, Baens M, Grosgeorge J, Rodgers K, Reid CDL, Dainton M, Dyer M, Fuzibet JG, Gratecos N, Tailan B, Ayraud N, Marynen P . Fluorescence in situ hybridization analysis of t(3;12)(q26;p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes Blood 1996 88: 682–689

    CAS  PubMed  Google Scholar 

  4. Peeters P, Wlodarska I, Baens M, Criel A, Selleslag D, Hagemeijer A, Van den Berghe H, Marynen P . Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders Cancer Res 1997 57: 564–569

    CAS  PubMed  Google Scholar 

  5. Secker-Walker LM, Mehta A, Bain B . Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group Study Br J Haematol 1995 91: 490–501

    Article  CAS  Google Scholar 

  6. Massaad L, Prieur M, Leonard C, Dutrillaux B . Biclonal chromosome evolution of chronic myelomonocytic leukemia in a child Cancer Genet Cytogenet 1990 44: 131–137

    Article  CAS  Google Scholar 

  7. Morishita K, Parganas E, Willman CL, Whittaker H, Drabkin H, Oval J, Taetle R, Valentine MB, Ihle JN . Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300–400 kilobases on chromosome band 3q26 Proc Natl Acad Sci USA 1992 89: 3937–3941

    Article  CAS  Google Scholar 

  8. Sitailo S, Sood R, Barton K, Nucifora G . Forced expression of the leukemia-associated gene EVI1 in ES cells: a model for myeloid leukemia with 3q26 rearrangements Leukemia 1999 13: 1639–1645

    Article  CAS  Google Scholar 

  9. Suwabe N, Takahashi S, Nakano T, Yamamoto M . GATA-1 regulates growth and differentiation of definitive erythroid lineage cells during in vitro ES cell differentiation Blood 1998 92: 4108–4118

    CAS  PubMed  Google Scholar 

  10. LaStarza R, Stella M, Testoni N, DiBona E, Ciolli S, Marynen P, Martelli MF, Mandelli F, Mecucci C . Characterization of 12p molecular events outside ETV6 in complete karyotypes of acute myeloid malignancies Br J Haematol 1999 107: 340–346

    Article  CAS  Google Scholar 

  11. Romana SP, Poirel H, Cella Valle V, Mauchauffe M, Busson-Le Coniat M, Berger R, Bernard OA . Molecular analysis of chromosomal breakpoints in three examples of chromosomal translocation involving the TEL gene Leukemia 1999 13: 1754–1759

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Academisch Ziekenhuis Groningen, The Netherlands

    AA van de Loosdrecht, MT Esselink, E Vellenga & GW van Imhoff

  2. Department of Medical Genetics, Rijks Universiteit Groningen, The Netherlands

    K Kok, B de Vries, AY van der Veen & E van den Berg

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

    P Marynen

Authors
  1. AA van de Loosdrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Kok
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B de Vries
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. AY van der Veen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E van den Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Marynen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Vellenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. GW van Imhoff
    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

van de Loosdrecht, A., Kok, K., de Vries, B. et al. Breakpoint analysis by fluorescence in situ hybridization in myelodysplastic syndromes with t(3;12)(q26;p13) and expression of EVI1. Leukemia 14, 1857–1858 (2000). https://doi.org/10.1038/sj.leu.2401895

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2401895

This article is cited by

Search

Advanced search

Quick links