Identification of the estrogen receptor beta as a possible new tamoxifen-sensitive target in diffuse large B-cell lymphoma

Myra Langendonk, Mathilde R W de Jong, Nienke Smit, Jonas Seiler, Bart Reitsma, Emanuele Ammatuna, Andor W J M Glaudemans, Anke van den Berg, Gerwin A Huls, Lydia Visser, Tom van Meerten*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

10 Citaten (Scopus)
85 Downloads (Pure)

Samenvatting

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Despite the proven efficacy of combined immunochemotherapy (R-CHOP) in the majority of patients, ~40% of DLBCL patients do not respond or will relapse and consequently have a very poor prognosis. The development of targeted therapies has not improved patient survival, underscoring the need for new treatment approaches. Using an unbiased genome-wide CD20 guilt-by-association approach in more than 1800 DLBCL patients, we previously identified the estrogen receptor beta (ERβ) as a new target in DLBCL. Here, we demonstrate that ERβ is expressed at significantly higher levels in DLBCL compared to normal B cells, and ERβ plays a role in the protection against apoptosis in DLBCL. Targeting of the ERβ with the selective estrogen receptor modulator tamoxifen reduces cell viability in all tested DLBCL cell lines. Tamoxifen-induced cell death was significantly decreased in an ERβ knock-out cell line. The activity of tamoxifen was confirmed in a xenograft human lymphoma model, as tumor growth decreased, and survival significantly improved. Finally, tamoxifen-treated breast cancer (BC) patients showed a significantly reduced risk of 38% for DLBCL compared to BC patients who did not receive tamoxifen. Our findings provide a rationale to investigate tamoxifen, a hormonal drug with a good safety profile, in DLBCL patients.

Originele taal-2English
Artikelnummer36
Aantal pagina's9
TijdschriftBlood cancer journal
Volume12
Nummer van het tijdschrift3
DOI's
StatusPublished - 7-mrt.-2022

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