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Quiescent leukaemic cells account for minimal residual disease in childhood lymphoblastic leukaemia

Leukemia volume 27, pages 1204–1207 (2013)Cite this article

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We investigated the cells responsible for MRD in childhood acute lymphoblastic leukaemia (cALL) (for patient information see Table 1), where molecular MRD monitoring has had a practise-changing impact.6 At presentation, cALLs comprise phenotypically distinct B-cell stages, including ProB-like (CD34+CD38+CD19+), and cells dubbed ‘Stem/B’ coexpressing stem (CD34+CD38−/low) and B-cell (CD19+) markers, seen only in leukaemia and pre-leukaemia.7, 8 Although recent studies suggest that cells capable of propagating cALL in xenografts are plastic and extend beyond the Stem/B compartment,9 its leukaemia-specificity provides a readily trackable biomarker in patients.

Table 1 cALL patient characteristics
Full size table

We first tracked the fate of leukaemic cells in MRD+ remission samples of three cALL patients who went on to relapse. In patient 1, BCR/ABL1+ ‘Stem/B’ cells selectively persisted at remission, when no BCR/ABL1+ leukaemic cells could be found in other B-cell compartments (Figures 1b and c). A similar picture emerged from the analysis of ProB-like and Stem/B cells in remission samples in two TEL/AML1 cases (patients 2 and 3; Figure 1d and Supplementary Figure 1A), suggesting that in patients with relapsed disease, cells within the Stem/B compartment are selectively chemoresistant, sustaining MRD and potentially initiating relapse.

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Acknowledgements

Leukaemia and Lymphoma Research (Specialist Programme Grant to TE), EuroCancerStemCell (6th framework EU Specific Targeted Research Projects to TE and SEJ), National Institute for Health Research Biomedical Research Centre Programme, CBRC, UCL, Haematolinne, IGA-MZ NT/12428-5, 00064203-FNM (JZ), a Deutsche Forschungsgemeinschaft fellowship LU1474/1-1 (CL) and a Career Development Programme fellowship from the Leukemia and Lymphoma Society, USA (PSW).

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Author notes

  1. S-E W Jacobsen and T Enver: These two authors contributed equally to this work.

  2. Current address: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

Authors and Affiliations

  1. The LLR John Barrington Laboratory, Cancer Institute, University College London, London, UK

    C Lutz, C Jensen & T Enver

  2. MRC MHU, WIMM, University of Oxford, Oxford, UK

    P S Woll, S A Clark, H Ferry, V Buckle & S-E W Jacobsen

  3. Haematopoietic Stem Cell Laboratory, WIMM, University of Oxford, Oxford, UK

    P S Woll, S A Clark, H Ferry & S-E W Jacobsen

  4. Department of Paediatric Haematology/Oncology, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK

    G Hall & C Mitchell

  5. Department of Paediatric Haematology, Lund University Hospital, Lund, Sweden

    A Castor

  6. Department of Haematology, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK

    H Dreau & A Schuh

  7. Centro Ricerca Tettamanti, Clinica Pediatrica Univ. Milano Bicocca, Ospedale San Gerardo, Monza, Italy

    G Cazzaniga & A Biondi

  8. Department of Paediatric Haematology/Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic

    J Zuna

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  1. C Lutz
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Corresponding authors

Correspondence to S-E W Jacobsen or T Enver.

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The authors declare no conflict of interest.

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Lutz, C., Woll, P., Hall, G. et al. Quiescent leukaemic cells account for minimal residual disease in childhood lymphoblastic leukaemia. Leukemia 27, 1204–1207 (2013). https://doi.org/10.1038/leu.2012.306

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