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Successful treatment of imatinib-resistant acute megakaryoblastic leukemia with e6a2 BCR/ABL: use of dasatinib and reduced-conditioning stem-cell transplantation

Leukemia volume 21, pages 2376–2377 (2007)Cite this article

Most hematological malignancies with BCR/ABL translocations express the fusion transcripts b2a2 (e13a2), b3a2 (e14a2) or e1a2, resulting in fusion proteins p210BCR/ABL or p190BCR/ABL. Atypical breakpoints in BCR may also be found. In the neutrophilic variant of chronic myeloid leukemia (CML), e19a2 transcripts result in a p230BCR/ABL fusion protein. Sporadic cases with b2a3 or b3a3 can also be found. The rare e6a2 transcript, resulting in a fusion protein of 185 kDa, has been reported in only eight cases and it has been suggested that e6a2 may confer a worse prognosis.1, 2, 3, 4, 5, 6, 7, 8 We described here a case of acute megakaryoblastic leukemia (AML) with the e6a2 transcript, successfully treated with dasatinib and reduced-conditioning allogeneic hematopoietic stem cell transplantation.

A 53-year-old woman was admitted in March 2005. She had a history of asthenia and abdominal pain over the previous few months. Her peripheral blood showed mild anemia and erythromyelemia. On referral, her performance status was 3, she had a fever of 39°C, plus splenomegaly and pleural effusion. Her white blood count was 23 × 109/l with 5% polymorphonuclear cells, 21% lymphocytes, 3% monocytes, 39% blasts, 16% basophils, 7% micromegakaryocytes and 7% erythromyelemia. Her bone marrow aspirate was hypocellular, with 32% blast cell infiltration and a negative peroxidase test. Blast cells were CD13+, CD31+, CD41+ and CD61+, suggesting megakaryoblastic AML. Bone marrow biopsy confirmed the diagnosis, with massive blastic infiltration and severe collagen fibrosis. Standard cytogenetic testing showed a 46, XX, t(9;22)(q34;q11), del(18)(p10) [15] karyotype. Molecular analysis showed no amplification product for primers detecting b2a2 and b3a2. Direct sequencing of the PCR product showed an e6a2 fusion transcript.

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References

  1. Hochhaus A, Reiter A, Skladny H, Melo JV, Sick C, Berger U et al. A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome-negative chronic myelogenous leukemia. Blood 1996; 88: 2236–2240.

    CAS  PubMed  Google Scholar 

  2. Dupont M, Jourdan E, Chiesa J . Identification of E6A2 BCR-ABL fusion in a Philadelphia-positive CML. Leukemia 2000; 14: 2011–2012.

    Article  CAS  Google Scholar 

  3. Schultheis B, Wang L, Clark RE, Melo JV . BCR-ABL with an e6a2 fusion in a CML patient diagnosed in blast crisis. Leukemia 2003; 17: 2054–2055.

    Article  CAS  Google Scholar 

  4. Colla S, Sammarelli G, Voltolini S, Crugnola M, Sebastio P, Giuliani N . e6a2 BCR-ABL transcript in chronic myeloid leukemia: is it associated with aggressive disease? Haematologica 2004; 89: 611–613.

    PubMed  Google Scholar 

  5. Hayette S, Tigaud I, Thomas X, French M, Perrin MC, Nicolini F et al. Identification of a rare e6a2 BCR-ABL fusion gene during the disease progression of chronic myelomonocytic leukemia: a case report. Leukemia 2004; 18: 1735–1736.

    Article  CAS  Google Scholar 

  6. Popovici C, Cailleres S, David M, Lafage-Pochitaloff M, Sainty D, Mozziconacci MJ . E6a2 BCR-ABL fusion with BCR exon 5-deleted transcript in a Philadelphia positive CML responsive to Imatinib. Leuk Lymphoma 2005; 46: 1375–1377.

    Article  CAS  Google Scholar 

  7. Roti G, La Starza R, Gorello P, Gottardi E, Crescenzi B, Martelli MF et al. e6a2 BCR/ABL1 fusion with cryptic der(9)t(9;22) deletions in a patient with chronic myeloid leukemia. Haematologica 2005; 90: 1139–1141.

    PubMed  Google Scholar 

  8. Gregoire MJ, Latger-Cannard V, Staal A, Bologna S, Leotard B, Rault JP et al. Identification of an acute basophilic leukaemia carrying a rare e6a2 BCR-ABL transcript. Acta Haematol 2006; 116: 216–218.

    Article  Google Scholar 

  9. Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 2007; 109: 3207–3213.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Service des Maladies du Sang, Centre Hospitalier et Universitaire de Lille, Lille, France

    S Corm & B Quesnel

  2. INSERM, U837, E3, Institut de Recherche sur le Cancer de Lille, Lille, France

    S Corm, A Renneville, N Grardel, C Preudhomme & B Quesnel

  3. IFR 114, Université de Lille 2, Lille, France

    S Corm, A Renneville, C Preudhomme & B Quesnel

  4. Laboratoire d'Hématologie, Centre Hospitalier et Universitaire de Lille, Lille, France

    A Renneville, N Grardel & C Preudhomme

  5. Service d'Oncologie médicale, Centre Hospitalier de Roubaix, Roubaix, France

    E Rad-Quesnel

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Corm, S., Renneville, A., Rad-Quesnel, E. et al. Successful treatment of imatinib-resistant acute megakaryoblastic leukemia with e6a2 BCR/ABL: use of dasatinib and reduced-conditioning stem-cell transplantation. Leukemia 21, 2376–2377 (2007). https://doi.org/10.1038/sj.leu.2404792

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