Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies

Its prevalence and clinical significance

Junji Hiraga, Akihiro Tomita, Takumi Sugimoto, Kazuyuki Shimada, Masafumi Ito, Shigeo Nakamura, Hitoshi Kiyoi, Tomohiro Kinoshita, Tomoki Naoe

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

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 downregulation of CD20 expression after rituximab treatment.

Original languageEnglish
Pages (from-to)4885-4893
Number of pages9
JournalBlood
Volume113
Issue number20
DOIs
Publication statusPublished - 19-11-2009
Externally publishedYes

Fingerprint

Chemotherapy
B-Cell Lymphoma
Combination Drug Therapy
Down-Regulation
Cells
Lymphoma, Large B-Cell, Diffuse
decitabine
Drug Therapy
Therapeutics
Salvaging
Messenger RNA
Follicular Lymphoma
Polymerase chain reaction
Transcription
Drug Delivery Systems
Rituximab
Epigenomics
Reverse Transcription
Restoration
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Hiraga, Junji ; Tomita, Akihiro ; Sugimoto, Takumi ; Shimada, Kazuyuki ; Ito, Masafumi ; Nakamura, Shigeo ; Kiyoi, Hitoshi ; Kinoshita, Tomohiro ; Naoe, Tomoki. / Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies : Its prevalence and clinical significance. In: Blood. 2009 ; Vol. 113, No. 20. pp. 4885-4893.
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Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies : Its prevalence and clinical significance. / Hiraga, Junji; Tomita, Akihiro; Sugimoto, Takumi; Shimada, Kazuyuki; Ito, Masafumi; Nakamura, Shigeo; Kiyoi, Hitoshi; Kinoshita, Tomohiro; Naoe, Tomoki.

In: Blood, Vol. 113, No. 20, 19.11.2009, p. 4885-4893.

Research output: Contribution to journalArticle

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T1 - Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies

T2 - Its prevalence and clinical significance

AU - Hiraga, Junji

AU - Tomita, Akihiro

AU - Sugimoto, Takumi

AU - Shimada, Kazuyuki

AU - Ito, Masafumi

AU - Nakamura, Shigeo

AU - Kiyoi, Hitoshi

AU - Kinoshita, Tomohiro

AU - Naoe, Tomoki

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