Skip to main content
SpringerLink
Log in

Monosomies 7p and 12p and FLT3 internal tandem duplication: possible markers for diagnosis of T/myeloid biphenotypic acute leukemia and its clonal evolution

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Biphenotypic acute leukemia co-expressing T-lymphoid and myeloid markers is rare, accounting for less than 1% of acute leukemias. However, several clinical characteristics including male predominance, frequent lymphadenopathy and unfavorable outcome have been identified. Recurrence of monosomies 7p and/or 12p in T/myeloid biphenotypic acute leukemia has been reported. We treated a patient with T/myeloid biphenotypic acute leukemia showing clonal chromosomal and genetic abnormalities including dic(7;12)(p11;p11) and Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication. Cytogenetic analysis of both bone marrow and lymph node cells disclosed that the patient’s lymph node leukemia cells had chromosomal abnormalities in addition to dic(7;12). Our findings suggest that the leukemia cells of systemic lymphadenopathy had evolved as secondary cells from marrow leukemia cells. The patient was successfully treated with induction chemotherapy for acute myeloid leukemia followed by allogeneic bone marrow transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization classification of tumours. Pathology and genetics of tumours of haemapoietic and lymphoid tissues. Lyon: IARC press; 2001.

    Google Scholar 

  2. Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias. European Group for the immunological characterization of leukemias (EGIL). Leukemia. 1995;9:1783–6.

    CAS  PubMed  Google Scholar 

  3. Buccheri V, Matutes E, Dyer MJ, Catovsky D. Lineage commitment in biphenotypic acute leukemia. Leukemia. 1993;7:919–27.

    CAS  PubMed  Google Scholar 

  4. Carbonell F, Swansbury J, Min T, et al. Cytogenetic findings in acute biphenotypic leukaemia. Leukemia. 1996;10:1283–7.

    CAS  PubMed  Google Scholar 

  5. Matutes E, Morilla R, Farahat N, et al. Definition of acute biphenotypic leukemia. Haematologica. 1997;82:64–6.

    CAS  PubMed  Google Scholar 

  6. Legrand O, Perrot JY, Simonin G, et al. Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression. Br J Haematol. 1998;100:147–55. doi:10.1046/j.1365-2141.1998.00523.x.

    Article  CAS  PubMed  Google Scholar 

  7. Przepiorka D, Weisdorf D, Martin P, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  8. Washington K, Bentley RC, Green A, Olson J, Treem WR, Krigman HR. Gastric graft-versus-host disease: a blinded histologic study. Am J Surg Pathol. 1997;21:1037–46. doi:10.1097/00000478-199709000-00008.

    Article  CAS  PubMed  Google Scholar 

  9. Cruz-Correa M, Poonawala A, Abraham SC, et al. Endoscopic findings predict the histologic diagnosis in gastrointestinal graft-versus-host disease. Endoscopy. 2002;34:808–13. doi:10.1055/s-2002-34257.

    Article  CAS  PubMed  Google Scholar 

  10. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10:1911–8.

    CAS  PubMed  Google Scholar 

  11. Rubio MT, Dhedin N, Boucheix C, et al. Adult T-biphenotypic acute leukaemia: clinical and biological features and outcome. Br J Haematol. 2003;123:842–9. doi:10.1046/j.1365-2141.2003.04715.x.

    Article  CAS  PubMed  Google Scholar 

  12. Killick S, Matutes E, Powles RL, et al. Outcome of biphenotypic acute leukemia. Haematologica. 1999;84:699–706.

    CAS  PubMed  Google Scholar 

  13. Tiribelli M, Damiani D, Masolini P, Candoni A, Calistri E, Fanin R. Biological and clinical features of T-biphenotypic acute leukaemia: report from a single centre. Br J Haematol. 2004;125:814–5. doi:10.1111/j.1365-2141.2004.04969.x.

    Article  PubMed  Google Scholar 

  14. Owaidah TM, Al Beihany A, Iqbal MA, Elkum N, Roberts GT. Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia. 2006;20:620–6. doi:10.1038/sj.leu.2404128.

    Article  CAS  PubMed  Google Scholar 

  15. Nakao M, Janssen JW, Erz D, Seriu T, Bartram CR. Tandem duplication of the FLT3 gene in acute lymphoblastic leukemia: a marker for the monitoring of minimal residual disease. Leukemia. 2000;14:522–4. doi:10.1038/sj.leu.2401695.

    Article  CAS  PubMed  Google Scholar 

  16. Yamamoto T, Isomura M, Xu Y, et al. PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia. Leuk Res. 2006;30:1085–9. doi:10.1016/j.leukres.2006.02.004.

    Article  CAS  PubMed  Google Scholar 

  17. Xu F, Taki T, Yang HW, et al. Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children. Br J Haematol. 1999;105:155–62. doi:10.1111/j.1365-2141.1999.01284.x.

    Article  CAS  PubMed  Google Scholar 

  18. Horiike S, Yokota S, Nakao M, et al. Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia. Leukemia. 1997;11:1442–6. doi:10.1038/sj.leu.2400770.

    Article  CAS  PubMed  Google Scholar 

  19. Lee JH, Min YH, Chung CW, et al. Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma. 2008;49:700–9. doi:10.1080/10428190701843247.

    Article  CAS  PubMed  Google Scholar 

  20. Gale RE, Hills R, Kottaridis PD, et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1,135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood. 2005;106:3658–65. doi:10.1182/blood-2005-03-1323.

    Article  CAS  PubMed  Google Scholar 

  21. Stirewalt DL, Kopecky KJ, Meshinchi S, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood. 2006;107:3724–6. doi:10.1182/blood-2005-08-3453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ponziani V, Gianfaldoni G, Mannelli F, et al. The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients. Leukemia. 2006;20:2074–6. doi:10.1038/sj.leu.2404368.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yosuke Matsumoto, Yoshiko Fujimoto, Kyoko Taniguchi, Daisuke Shimizu, Kazuho Shimura, Hitoji Uchiyama, Junya Kuroda, Kenichi Nomura, Chihiro Shimazaki, Shigeo Horiike & Masafumi Taniwaki

  2. Department of Molecular Laboratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Tomohiko Taki, Daisuke Shimizu, Tohru Inaba & Masafumi Taniwaki

Authors
  1. Yosuke Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomohiko Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshiko Fujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyoko Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daisuke Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazuho Shimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hitoji Uchiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Junya Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kenichi Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tohru Inaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chihiro Shimazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shigeo Horiike
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Masafumi Taniwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yosuke Matsumoto.

About this article

Cite this article

Matsumoto, Y., Taki, T., Fujimoto, Y. et al. Monosomies 7p and 12p and FLT3 internal tandem duplication: possible markers for diagnosis of T/myeloid biphenotypic acute leukemia and its clonal evolution. Int J Hematol 89, 352–358 (2009). https://doi.org/10.1007/s12185-009-0268-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-009-0268-7

Keywords

Search

Navigation