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Identification of e19a2 BCR–ABL fusions (μ-BCR breakpoints) at the DNA level by ligation-mediated PCR

Leukemia volume 19, pages 1292–1295 (2005)Cite this article

TO THE EDITOR

The Philadelphia chromosome (Ph) derives from a balanced translocation between chromosomes 9 and 22, and results in a BCR–ABL fusion gene. In the vast majority of Ph+ leukemias, breakpoints in the ABL gene are distributed over a ∼200 kb breakpoint region between exons 1b and a2, while breakpoints in the BCR gene are clustered in three well-defined regions.1 The major breakpoint cluster region (M-BCR) is a ∼2.9 kb chromosomal region between exons 13 and 15.1 The breakpoint can be detected in more than 95% of chronic myeloid leukemia (CML) and can lead to two types of mRNA molecules (e13a2 or e14a2, formerly assigned as b2a2 and b3a2), both encoding a p210BCR–ABL fusion protein. The minor breakpoint cluster region (m-BCR) spans a ∼55 kb intronic sequence between the two alternative exons 1 and 2. The corresponding e1a2 fusion gene transcript encodes the p190BCR–ABL fusion protein and is frequently associated with Ph+ acute lymphoblastic leukemia. The micro-breakpoint cluster region (μ-BCR) spans a ∼1 kb sequence which is located in intron 19 of the BCR gene. The corresponding fusion gene transcript e19a2 results in a 230 kDa protein. The e19a2 fusion gene was initially described to be associated with neutrophilic-CML (N-CML), a mild Ph+ myeloproliferative disease with only rarely progression, but in later reports e19a2 fusion gene transcripts were also found in classical CML and in acute myeloid leukemia (AML).2, 3

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Acknowledgements

We are grateful to Professor Dr N Blanckaert for the continuous support, to Annemarie Wijkhuijs and Daniëlle Jacobs for their technical assistance and to Marieke Comans-Bitter for preparation of the figures. We thank Dr Hiroshi Wada who kindly donated the AR230 cell line. This work was supported by a grant of the IGA MZ CR: NC/7560-3.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Laboratory of Haematology, University Hospital Gasthuisberg, Leuven, Belgium

    N Boeckx

  2. Department of Immunology, Erasmus MC, Rotterdam, The Netherlands

    M W J C Jansen, V H J van der Velden & J J M van Dongen

  3. Institute of Haematology and Blood Transfusion, Prague, Czech Republic

    C Haskovec

  4. Department of Human Genetics, KU Leuven, Leuven, Belgium

    P Vandenberghe

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  1. N Boeckx
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Correspondence to J J M van Dongen.

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Boeckx, N., Jansen, M., Haskovec, C. et al. Identification of e19a2 BCR–ABL fusions (μ-BCR breakpoints) at the DNA level by ligation-mediated PCR. Leukemia 19, 1292–1295 (2005). https://doi.org/10.1038/sj.leu.2403761

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