Identification of the estrogen receptor beta as a possible new tamoxifen-sensitive target in diffuse large B-cell lymphoma.
Myra LangendonkMathilde R W de JongNienke SmitJonas SeilerBart ReitsmaEmanuele AmmatunaAndor W J M GlaudemansAnke van den BergGerwin A HulsLydia VisserTom van MeertenPublished in: Blood cancer journal (2022)
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.
Keyphrases
- diffuse large b cell lymphoma
- estrogen receptor
- end stage renal disease
- epstein barr virus
- newly diagnosed
- chronic kidney disease
- ejection fraction
- cell death
- breast cancer cells
- poor prognosis
- genome wide
- type diabetes
- patient reported outcomes
- oxidative stress
- endothelial cells
- gene expression
- adipose tissue
- dna methylation
- skeletal muscle
- case report
- endoplasmic reticulum
- adverse drug
- replacement therapy