Journal of Hematopathology

, Volume 7, Issue 2, pp 71–77 | Cite as

ETV6/FLT3 fusion in a mixed-phenotype acute leukemia arising in lymph nodes in a patient with myeloproliferative neoplasm with eosinophilia

  • Niloufar Hosseini
  • Kenneth J. Craddock
  • Shabnam Salehi-rad
  • Shawn Brennan
  • Denis J. Bailey
  • Joseph M. Brandwein
  • Anna Porwit
Case Report

Abstract

The ETV6/FLT3 fusion gene has been recently reported in association with myeloproliferative neoplasm with eosinophilia (MPN-Eo) and peripheral T cell lymphoma. Favorable clinical response to a targeted FLT3 tyrosine kinase inhibitor (FLT3 TKI) was noted. Here we report a novel phenotype associated with ETV6/FLT3 rearrangement, in a 38-year-old female with presentation of progressive lymphadenopathy. Lymph node biopsy showed mixed-phenotype acute leukemia (MPAL) with expression of T cell and myeloid markers. Bone marrow morphology was consistent with MPN-Eo and no evidence of MPAL. Karyotype analysis revealed 46, XX, t(12;13)(p13;q12). ETV6/FLT3 fusion was demonstrated by fluorescence in situ hybridization. This is the first report of ETV6/FLT3 rearrangement showing a phenotype of extramedullary T/myeloid MPAL arising in the setting of MPN-Eo. We suggest addition of this entity to the WHO category of “myeloid/lymphoid neoplasms with eosinophilia,” particularly given the possibility of clinical response to FLT3 TKI in MPAL, a disease usually associated with poor prognosis.

Keywords

ETV6 FLT3 Mixed-lineage acute leukemia Myeloproliferative disorders 

References

  1. 1.
    Bain BJ, Gilliland DG, Horny HP et al (2008) Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. In: Swerdlow SH, Campo E, Harris NL (eds) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. IARC, Lyon, pp 68–73Google Scholar
  2. 2.
    Cools J, DeAngelo DL, Gotlib J et al (2003) A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348(13):1201–1214PubMedCrossRefGoogle Scholar
  3. 3.
    Vu HA, Xinh PT, Masuda M et al (2006) FLT3 is fused to ETV6 in a myeloproliferative disorder with hypereosinophilia and a t(12;13)(p13;q12) translocation. Leukemia 20:1414–1421PubMedCrossRefGoogle Scholar
  4. 4.
    Walz C, Erben P, Ritter M et al (2011) Response of ETV6-FLT3-positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3. Blood 118:2239–2242PubMedCrossRefGoogle Scholar
  5. 5.
    Kantarjian HM, O’Brien S, Smith TL et al (2000) Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 18:547–561PubMedGoogle Scholar
  6. 6.
    Lichter P, Cremer T (1992) Chromosome analysis by non-isotopic in situ hybridization. In: Rooney DE, Czepulkowski BH (eds) Human cytogenetics: a practical approach, 2nd edn. Oxford University Press, New York, p 157Google Scholar
  7. 7.
    Metzgeroth G, Walz C, Erben P et al (2008) Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome: a phase-II study. Br J Haematol 143(5):707–715PubMedCrossRefGoogle Scholar
  8. 8.
    David M, Cross NC, Burgstaller S et al (2007) Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 109(1):61–64PubMedCrossRefGoogle Scholar
  9. 9.
    De Braekeleer E et al (2012) ETV6 fusion genes in hematological malignancies: a review. Leuk Res 36(8):945–961PubMedCrossRefGoogle Scholar
  10. 10.
    Jackson CC, Medeiros LJ, Miranda RN (2010) 8p11 myeloproliferative syndrome: a review. Hum Pathol 41(4):461–476PubMedCrossRefGoogle Scholar
  11. 11.
    Huang Q, Snyder DS, Chu P et al (2011) PDGFRA rearrangement leading to hyper-eosinophilia, T-lymphoblastic lymphoma, myeloproliferative neoplasm and precursor B-cell acute lymphoblastic leukemia. Leukemia 25(2):371–375PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Niloufar Hosseini
    • 1
  • Kenneth J. Craddock
    • 1
  • Shabnam Salehi-rad
    • 1
  • Shawn Brennan
    • 1
  • Denis J. Bailey
    • 1
  • Joseph M. Brandwein
    • 2
  • Anna Porwit
    • 1
  1. 1.Department of Pathology, Toronto General Hospital, University Health NetworkUniversity of TorontoTorontoCanada
  2. 2.Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health NetworkUniversity of TorontoTorontoCanada

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