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An unrelated cytogenetic karyotype and intra-lineage shift at relapse of an aggressive paediatric B-precursor ALL

Leukemia volume 16, pages 2337–2339 (2002)Cite this article

Cytogenetic analysis of B-precursor ALL at presentation and subsequent relapse frequently reveals subclonal evolution and increasing karyotypic complexity. The emergence of an entirely independent cytogenetically abnormal clone at relapse compared with presentation, however, is an extremely rare event in both paediatric and adult ALL.1 In fact, a proportion of those rare cases show the emergence of 11q23 abnormalities, and presumed MLL gene rearrangement, during disease progression which, in non-infant cases, is more likely to represent DNA-topoisomerase II inhibitor-induced secondary leukaemia rather than relapse of the primary disease.1 Minor alterations in immunophenotype are a relatively more common feature of this malignancy, although only 10% of cases exhibit intra-lineage shifts between presentation and relapse.2

We report the unusual case of a B-precursor ALL exhibiting both an intra-lineage shift and a complete change in cytogenetic karyotype between diagnosis and relapse. A 12-year-old girl presented with lethargy, shortness of breath, weight loss and pallor. Investigations revealed a white cell count (WCC) of 58.9 × 109/l, haemaglobin (Hb) at 2.6 g/dl and platelets at 70 × 109/l, with numerous blast cells on the peripheral blood smear. A marrow aspirate confirmed the diagnosis of acute lymphoblastic leukaemia (FAB type L1). Immunophenotyping of the diagnostic bone marrow sample showed a pre-B ALL phenotype that was surface positive for CD19, CD22, CD24, HLA-DR, CD45 and weakly positive for CD5; surface negative for CD10, CD79b, CD34, CD13 and CD33; cytoplasmic μ positive and nuclear TdT negative. Analysis of G-banded chromosomes from diagnosis identified eight metaphase cells with a pseudo-diploid karyotype of 46,XX,add(2)(q3?),del(6)(q1?),add(9)(p?2) and two cells exhibiting an apparently normal female karyotype. Additional interphase and metaphase FISH analyses were performed (Leukaemia Research Fund ALL Database Laboratory, Royal Free Hospital, London, UK) and showed no evidence of a TEL/AML1 or MLL gene rearrangement at diagnosis. Furthermore, the presence of a cytogenetically cryptic BCR/ABL rearrangement was excluded by RT-PCR. The patient was treated according to the Medical Research Council (MRC) ALL97 high risk protocol and was randomised to receive prednisolone, cranial radiotherapy and 6-mercaptopurine.

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Authors and Affiliations

  1. Cancer Research UK Institute for Cancer Studies, Birmingham University, UK

    VJ Weston & T Stankovic

  2. West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, UK

    DJ McMullan

  3. Department of Clinical Immunology, Birmingham Medical School, UK

    M Drayson

  4. Department of Paediatrics, North Staffordshire Hospital, UK

    BE Ley

  5. Department of Haematology, Birmingham Children's Hospital, UK

    S Lawson & FGH Hill

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  1. VJ Weston
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  2. T Stankovic
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Weston, V., Stankovic, T., McMullan, D. et al. An unrelated cytogenetic karyotype and intra-lineage shift at relapse of an aggressive paediatric B-precursor ALL. Leukemia 16, 2337–2339 (2002). https://doi.org/10.1038/sj.leu.2402689

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