CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure

Johnson, Nathalie A.; Leach, Stephen; Woolcock, Bruce W.; deLeeuw, Ronald J.; Bashashati, Ali; Sehn, Laurie H.; Connors, Joseph M.; Chhanabhai, Mukesh; Brooks‐Wilson, Angela; Gascoyne, Randy D.

doi:10.3324/haematol.2008.001024

Cited by 56 publications

(43 citation statements)

References 21 publications

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“…Interestingly, the relative frequency of the cases that showed discordant CD20 expression was also higher in the recurrent group. Loss of CD20 expression at relapse was reported in patients, who received Rituximab contained chemotherapy, genetic and epigenetic mechanisms have been suggested Johnson et al 2009, Terui et al 2009). Discrepancy of CD20 expression between FCM and IHC was occurred more frequently in de novo DLBCL than in recurrent cases (Johnson et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Loss of CD20 expression at relapse was reported in patients, who received Rituximab contained chemotherapy, genetic and epigenetic mechanisms have been suggested Johnson et al 2009, Terui et al 2009). Discrepancy of CD20 expression between FCM and IHC was occurred more frequently in de novo DLBCL than in recurrent cases (Johnson et al 2009). One of the reasons for the discrepancy is that the expression of CD20 on the cell surface was lost due to C-terminal deletion of CD20 (Terui et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports indicate that loss of CD20 expression occurs in some patients with B-cell lymphomas during rituximab therapy, but the incidence has not been clarified Johnson et al 2009). We showed significantly higher rate for loss of CD20 expression by IHC in the recurrent cases (15.7%, 16/102 cases) than in newly diagnosed cases (3.4%, 29/854 cases) in this largest scale of analysis among the previous reports.…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathological Features of Malignant Lymphoma in Japan: The Miyagi Study

Miura

Fukuhara

Yamamoto

et al. 2011

Tohoku J. Exp. Med.

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The Miyagi Study is an epidemiological study of malignant lymphoma, including immunological and genetic analyses, constructed by a population-based registration system covering Miyagi prefecture, Japan. A total of 1,552 newly diagnosed cases in Miyagi between 2002 and 2008 were enrolled in this study; 75% were B-cell lymphomas, 19% were T-cell and natural killer-cell (T/NK-cell) lymphomas, and 5% were Hodgkin's lymphomas. The most frequent subtype of B-cell lymphoma is diffuse large B-cell lymphoma, followed by follicular lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (51%, 24% and 8%, respectively). Thus, follicular lymphoma accounts for 18.2% of newly diagnosed cases in Miyagi; unexpectedly, its frequency is similar to that reported in Western countries. The common subtypes of T/NK-cell lymphoma are peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and adult T-cell leukemia/lymphoma (30%, 15% and 14%, respectively). Most of the data are similar to those reported in Asian countries, except for follicular lymphoma. We also analyzed the CD20 expression in B-cell lymphomas by flow cytometry for the cell membrane expression and by immunohistochemistry for the cytoplasmic expression. The cell membrane expression of CD20 protein may determine the susceptibility of B-cell lymphomas to anti-CD20 antibody therapy. The lack of CD20 expression was confirmed by both methods in 4 cases of 585 newly diagnosed cases (0.7%) and in 5 of 67 recurrent cases (7.5%). Furthermore, 23 cases (6.5%) showed the discrepancy of CD20 expression between both methods. The Miyagi Study has revealed the latest epidemiological features of malignant lymphoma in Japan.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Clinicopathological Features of Malignant Lymphoma in Japan: The Miyagi Study

Miura

Fukuhara

Yamamoto

et al. 2011

Tohoku J. Exp. Med.

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“…Rituximab is reported to bind to extracellular proteins of ANPS at positions 170 to 173 and YCYSI at positions 182 to 185 included in exon 5 of the MS4A1 gene. (17,18) The B-ly1 antibody targets the same amino acid sequence on the extracellular CD20 epitope as rituximab. (18,19) Antibody L26 recognizes an intracellular epitope on the CD20 antigen that includes sequences encoded by exons 3, 5, 7, or 8.…”

Section: Discussionmentioning

confidence: 99%

“…(17,18) The B-ly1 antibody targets the same amino acid sequence on the extracellular CD20 epitope as rituximab. (18,19) Antibody L26 recognizes an intracellular epitope on the CD20 antigen that includes sequences encoded by exons 3, 5, 7, or 8. (20) The correlation of expression of these different epitopes of CD20 in this study suggests that CD20 reduction is caused not by a particular gene deletion or mutation but by pre-or posttranscriptional abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Comparison of CD20 expression in B‐cell lymphoma between newly diagnosed, untreated cases and those after rituximab treatment

Miyoshi¹,

Sato

Kimura³

et al. 2012

Cancer Science

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Few studies have statistically investigated reduced CD20 expression in B‐cell lymphoma after rituximab therapy and genomic mutation of CD20 associated with reduction. We examined CD20‐positive rate in follicular lymphoma (FL) and diffuse large B‐cell lymphoma (DLBCL) by flow cytometry (FCM) and immunohistochemical staining (IHS), comparing 138 cases after rituximab therapy with 360 initial, not yet treated cases. Sequence analysis of exons 3 to 8 of CD20 was performed on 22 cases with low CD20‐positive rate after rituximab treatment. The results showed a statistical correlation between CD20‐positive rate in FCM and IHS. By FCM, the CD20‐positive rate among post‐rituximab cases was significantly lower than among initial cases in DLBCL, non‐germinal center origin B‐cell type (average values [avg] 57.8 and 87.9, respectively) (P < 0.0001), FL2 (avg, 93.9; 103.2) (P = 0.0083), and FL3A (avg, 90.6; 100.7) (P = 0.033). Stratified analyses of post‐rituximab cases showed significantly lower CD20‐positive rate in cases that were resistant at the start of the treatment and cases with progressive disease during rituximab therapy before biopsy. Sequence analysis showed silent mutation of exon 4 (632 C/T) in seven cases, although this number was not statistically significant. These results suggest the influence of B‐lymphoma subtype and a therapeutic effect before biopsy on CD20 expression at relapse and contribute to a better therapeutic approach for relapse cases after rituximab therapy. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02307.x, 2012)

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Pharmacology to Practice

Lue,

Cheson

2024

Precision Cancer Therapies Vol 2 ‐ Immunologic Approaches for the Treatment of Lymphoid Malignancies ‐ From Concept to Practice

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CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure

Cited by 56 publications

References 21 publications

Clinicopathological Features of Malignant Lymphoma in Japan: The Miyagi Study

Clinicopathological Features of Malignant Lymphoma in Japan: The Miyagi Study

Comparison of CD20 expression in B‐cell lymphoma between newly diagnosed, untreated cases and those after rituximab treatment

Pharmacology to Practice

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