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e19a2-positive chronic myeloid leukaemia with BCR exon e16-deleted transcripts

Leukemia volume 16, pages 1562–1563 (2002)Cite this article

The Philadelphia (Ph) chromosome which characterises chronic myeloid leukaemia (CML) is created by a balanced reciprocal t(9;22)(q34;q11) translocation, in which the ABL and BCR genes are disrupted, to form a BCR-ABL fusion gene. In the vast majority of cases, the breakpoints in the BCR gene on chromosome 22 are in the major breakpoint cluster region (M-bcr), a 5.8 kilobase (kb) region spanning 5 exons originally designated b1-b5 (now also designated e12-e16). Rare cases of CML have a BCR breakpoint considerably more 3′ than M-BCR, located in the (-bcr region, resulting in an e19a2 fusion transcript, which encodes for a longer 230 kDa BCR-ABL protein. e19a2 CML has been associated with chronic neutrophilic leukaemia (CNL). CNL is a rare myeloproliferative disorder which is typified by a lower peripheral blood (PB) white count, a lower proportion of PB neutrophil precursors, less severe anaemia, and less prominent splenomegaly at initial presentation, and a lower probability of disease progression.1 We now report two cases of e19a2-positive CML, in which a variant BCR-ABL transcript was identified containing an in-frame deletion of the whole of exon e16. Such a rearrangement has not to our knowledge been previously reported.

A 52-year-old previously healthy woman was diagnosed with CML in July 1996. The white blood cell count at diagnosis was 450 × 109/l, with a differential of 36% neutrophils, 2% lymphocytes, 2% monocytes, 3% eosinophils, 1% basophils, 28% metamyelocytes, 10% myelocytes, 5% promyelocytes, 13% blasts, and the haemoglobin concentration was 8.7 g/dl. The spleen was 4 cm below the costal margin. At this time all 10 metaphases examined showed 47XX,t(9,22)(q34;q11), +der(22)t(9;22)(q34;q11). She was initially treated with hydroxyurea and interferon, but did not achieve a cytogenetic response after 7 months of treatment and interferon was discontinued. She developed lymphoid blast crisis in April 1998, and marrow cytogenetics at that time revealed an additional clone with a complex karyotype including deletions in 3p and 6q, and monosomy 7. She achieved a second chronic phase (CP) after treatment with vincristine and prednisolone. She received ALL maintenance chemotherapy until November 1998, when she developed a second lymphoid blast crisis, associated with the same complex karyotype. Following treatment with daunorubicin, vinblastine and steroids she achieved a third CP. She underwent transplantation in March 1999, using standard BuCy conditioning and with cryopreserved autologous first CP stem cells as the graft. On haemopoietic recovery she was maintained on hydroxyurea alone. In December 2000, all 30 metaphases examined showed 47XX,t(9,22)(q34;q11), +der(22)t(9;22)(q34;q11), with no evidence of the complex karyotype associated with the blast crisis.

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Authors and Affiliations

  1. Department of Haematology, University of Liverpool, UK

    L Wang & RE Clark

  2. Haematology Department, Ysbyty Gwynedd, Bangor, North Wales, UK

    J Seale

  3. Haematology Department, Southport General Hospital, Southport, UK

    BE Woodcock

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  1. L Wang
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  2. J Seale
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  4. RE Clark
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Wang, L., Seale, J., Woodcock, B. et al. e19a2-positive chronic myeloid leukaemia with BCR exon e16-deleted transcripts. Leukemia 16, 1562–1563 (2002). https://doi.org/10.1038/sj.leu.2402600

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