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Kinetics of humoral response to ALK and its relationship with minimal residual disease in pediatric ALCL

Leukemia volume 23, pages 400–402 (2009)Cite this article

Anaplastic large-cell lymphoma (ALCL) makes up approximately 15% of pediatric non-Hodgkin's lymphoma (NHL) and the vast majority of them is associated with the t(2;5) translocation that results in the expression of a hybrid oncogenic tyrosine kinase. It consists of the amino terminus of the nuclear protein nucleophosmin (NPM) fused to the intracytoplasmic region of the anaplastic lymphoma kinase (ALK) that impacts many cellular responses including proliferation, growth and apoptosis.1 In addition to its direct effects of ALK on signal transduction pathways, ALK overexpression may also induce a host immune reaction, giving rise to autologous anti-ALK antibodies in patients with ALK-positive ALCL. Circulating antibodies against NPM-ALK were originally reported in 11 ALK-positive ALCL patients using an immunocytochemical approach.2 In that study, no conclusions concerning the clinical significance of anti-NPM-ALK antibodies could be drawn, due to the small number of patients; however, a tendency to higher antibody levels in pretreatment blood samples was observed.

Recently, we demonstrated that minimal bone marrow (BM) involvement at diagnosis is a common event in pediatric ALCL and that minimal BM disease monitoring can identify patients at risk of relapse.3 In addition, Damm-Welk et al.4 showed that patients with more than 10 normalized copy numbers (NCNs) NPM-ALK in BM had a cumulative incidence of relapse (CI-R) of 71±14% compared with CI-R of 18±6% for patients with 10 or fewer NCNs (P<0.001) and that quantitative PCR for NPM-ALK in BM and peripheral blood (PB) is highly concordant.

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Acknowledgements

This work was supported by Fondazione Città della Speranza.

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Authors and Affiliations

  1. Dipartimento di Pediatria, Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera, Università di Padova, Padua, Italy

    L Mussolin, M Pillon, G Tridello & A Rosolen

  2. IOV (Istituto Oncologico Veneto-IRCCS, Padova), Padua, Italy

    P Bonvini

  3. Nuffeld Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK

    K Ait-Tahar & K Pulford

  4. Dipartimento di Pediatria, Unità di Emato-oncologia Pediatrica, Ospedale Pausilipon, Naples, Italy

    S Buffardi

  5. Dipartimento di Pediatria, Clinica di Ematologia Pediatrica, Ospedale Bambino Gesù, Rome, Italy

    A Lombardi

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  1. L Mussolin
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  2. P Bonvini
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  8. K Pulford
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  9. A Rosolen
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Correspondence to A Rosolen.

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Mussolin, L., Bonvini, P., Ait-Tahar, K. et al. Kinetics of humoral response to ALK and its relationship with minimal residual disease in pediatric ALCL. Leukemia 23, 400–402 (2009). https://doi.org/10.1038/leu.2008.184

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