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Blood, 14 May 2009, Vol. 113, No. 20, pp. 4885-4893. Prepublished online as a Blood First Edition Paper on February 26, 2009; DOI 10.1182/blood-2008-08-175208. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2008-08-175208v1 113/20/4885    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hiraga, J. Articles by Naoe, T. Search for Related Content PubMed PubMed Citation Articles by Hiraga, J. Articles by Naoe, T. Related Collections Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance Junji Hiraga1,2, Akihiro Tomita1, Takumi Sugimoto1, Kazuyuki Shimada1, Masafumi Ito3, Shigeo Nakamura4, Hitoshi Kiyoi5, Tomohiro Kinoshita1, and Tomoki Naoe1 1 Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya; 2 Department of Hematology, Toyota Memorial Hospital, Toyota; 3 Department of Pathology, Japanese Red Cross, Nagoya First Hospital, Nagoya; 4 Department of Pathology and Clinical Laboratories, Nagoya University Hospital, Nagoya; and 5 Department of Infectious Diseases, Nagoya University School of Medicine, Nagoya, Japan Although rituximab is a key molecular targeting drug for CD20-positive B-cell lymphomas, resistance to rituximab has recently been recognized as a considerable problem. Here, we report that a CD20-negative phenotypic change after chemotherapies with rituximab occurs in a certain number of CD20-positive B-cell lymphoma patients. For 5 years, 124 patients with B-cell malignancies were treated with rituximab-containing chemotherapies in Nagoya University Hospital. Relapse or progression was confirmed in 36 patients (29.0%), and a rebiopsy was performed in 19 patients. Of those 19, 5 (26.3%; diffuse large B-cell lymphoma [DLBCL], 3 cases; DLBCL transformed from follicular lymphoma, 2 cases) indicated CD20 protein-negative transformation. Despite salvage chemotherapies without rituximab, all 5 patients died within 1 year of the CD20-negative transformation. Quantitative reverse-transcription–polymerase chain reaction (RT-PCR) showed that CD20 mRNA expression was significantly lower in CD20-negative cells than in CD20-positive cells obtained from the same patient. Interestingly, when CD20-negative cells were treated with 5-aza-2'-deoxycytidine in vitro, the expression of CD20 mRNA was stimulated within 3 days, resulting in the restoration of both cell surface expression of the CD20 protein and rituximab sensitivity. These findings suggest that some epigenetic mechanisms may be partly related to the down-regulation of CD20 expression after rituximab treatment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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