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A new case with rare e6a2 BCR–ABL fusion transcript developing two new resistance mutations during imatinib mesylate, which were replaced by T315I after subsequent dasatinib treatment

Leukemia volume 22, pages 856–858 (2008)Cite this article

The BCR–ABL fusion in chronic myeloid leukemia (CML) is represented in approximately 95% of all CML by the b2a2- and the b3a2-fusion transcripts (M–BCR), whereas the b2a3-, b3a3-, e1a2-, e19a2- and other rare fusions each account for less than 1%.1 One of the rare fusion transcript types is the e6a2 with breakpoint in intron 6 of BCR. So far, this fusion type was reported in 10 CML cases and in one T-acute lymphoblastic leukemia (T-ALL) case only.2, 3, 4 Here we contribute another case of e6a2 in chronic phase of CML which developed resistance to imatinib and subsequent dasatinib treatment.

However, after 5 months of dasatinib, peripheral blood again showed an increase of leukocytes (15.1 × 109 l−1 and loss of hematological remission. Cytogenetics revealed 18/20 Ph+ bone marrow metaphases (interphase FISH: 60/100 BCR–ABL+ nuclei; BCR–ABL/ABL 0.325 similar to the diagnostic value). Mutation analysis showed reduction of the K245E and L284S mutated clones below the detection level. Instead, a T315I mutation was detected in almost 100% of all fusion transcripts. This mutation is known to confer resistance to imatinib, dasatinib and nilotinib. The patient rapidly progressed to blast crisis and died. The originally planned allogeneic stem cell transplantation could not be performed (Table 1).

Table 1 Cytomorphology, cytogenetics, interphase FISH, and PCR results of bone marrow (BM) and peripheral blood (PB) analyses during follow-up of imatinib and dasatinib treatment
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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, Munich, Germany

    S Schnittger, W Kern, T Haferlach & C Haferlach

  2. Stem Cell Transplantation, University Hospital of Hamburg-Eppendorf, Martinistr. 52, Hamburg, Germany

    U Bacher

  3. Medical Department I, Klinikum Bremen-Mitte, St Juergenstr. 1, Bremen, Germany. E-mail: susanne.schnittger@mll-online.com,

    B Hertenstein

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Schnittger, S., Bacher, U., Kern, W. et al. A new case with rare e6a2 BCR–ABL fusion transcript developing two new resistance mutations during imatinib mesylate, which were replaced by T315I after subsequent dasatinib treatment. Leukemia 22, 856–858 (2008). https://doi.org/10.1038/sj.leu.2404949

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