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Blood, 15 November 2008, Vol. 112, No. 10, pp. 3982-3988. Prepublished online as a Blood First Edition Paper on September 9, 2008; DOI 10.1182/blood-2008-06-164129. This Article Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2008-06-164129v1 112/10/3982    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dworzak, M. N. Articles by Gadner, H. Search for Related Content PubMed PubMed Citation Articles by Dworzak, M. N. Articles by Gadner, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 19, 2008 Accepted August 15, 2008 CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immuno-therapy Michael N. Dworzak*, Angela Schumich, Dieter Printz, Ulrike Potschger, Zvenyslava Husak, Andishe Attarbaschi, Giuseppe Basso, Giuseppe Gaipa, Richard Ratei, Georg Mann, and Helmut Gadner Children's Cancer Research Institute, Vienna, Austria St. Anna Children's Hospital, Vienna, Austria Laboratory of Pediatric Onco-Hematology, Department of Pediatrics, University Hospital of Padova, Padova, Italy Tettamanti Research Center, Department of Pediatrics, University Milano-Bicocca, Ospedale San Gerardo, Monza, Italy Department of Hematology, Oncology and Tumor Immunology, Robert-Roessle-Clinic, HELIOS Klinikum Berlin, Charite Medical School, Berlin, Germany * Corresponding author; email: dworzak{at}stanna.at. CD20 is expressed in about one half of pediatric acute lymphoblastic leukemia (ALL) cases with B-cell precursor (BCP) origin. We observed recently that it is further up-regulated in some patients during induction treatment. To understand the impact of this on the potential effectiveness of anti-CD20 immunotherapy, we studied 237 CD10-positive pediatric BCP-ALL patients consecutively recruited to trial AIEOP-BFM-ALL-2000. We analyzed CD20 expression changes from diagnosis to end-induction, focusing on sample pairs with 0.1% residual leukemic blasts (MRD), and assessed complement-induced cytotoxicity by CD20-targeting with rituximab in-vitro (n=9 paired samples). CD20-positivity significantly increased from 45% in initial samples to 81% at end-induction (day 15: 71%). Also the levels of expression increased, so that 52% of cases at end-induction showed 90% CD20pos leukemic cells, as opposed to 5% at diagnosis (day 15: 20%). CD20 up-regulation was frequent in high-risk patients, patients with high MRD at end-induction, and patients who suffered later from relapse, but not in TEL/AML1 cases. Notably, up-regulation occurred in viable cells sustaining chemotherapy. In-vitro, CD20 up-regulation significantly enhanced rituximab-cytotoxicity and could be elicited upon prednisolone incubation. In summary, CD20 up-regulation is frequently induced in BCP-ALL during induction and this translates into an acquired state of higher sensitivity to rituximab. This study was registered at http://www.clinicaltrials.gov/ as NCT00430118. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Irving, J. Jesson, P. Virgo, M. Case, L. Minto, L. Eyre, N. Noel, U. Johansson, M. Macey, L. Knotts, et al. Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting; Haematologica, June 1, 2009; 94(6): 870 - 874. [Abstract] [Full Text] [PDF]

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