High CXCR4 expression impairs rituximab response and the prognosis of R-CHOP-treated diffuse large B-cell lymphoma patients.
Oncotarget
; 10(7): 717-731, 2019 Jan 22.
Article
en En
| MEDLINE
| ID: mdl-30774774
ABSTRACT
Survival of diffuse large B-cell lymphoma (DLBCL) patients has improved by inclusion of rituximab. Refractory/recurrent disease caused by treatment resistance is, however, a major problem. Determinants of rituximab sensitivity are not fully understood, but effect of rituximab are enhanced by antagonizing cell surface receptor CXCR4. In a two-step strategy, we tested the hypothesis that prognostic value of CXCR4 in DLBCL relates to rituximab treatment, due to a hampering effect of CXCR4 on the response of DLBCL cells to rituximab. First, by investigating the prognostic impact of CXCR4 mRNA expression separately for CHOP (n=181) and R-CHOP (n=233) cohorts and, second, by assessing the interaction between CXCR4 and rituximab in DLBCL cell lines. High CXCR4 expression level was significantly associated with poor outcome only for R-CHOP-treated patients, independent of IPI score, CD20 expression, ABC/GCB and B-cell-associated gene signature (BAGS) classifications. s. For responsive cell lines, inverse correlation was observed between rituximab sensitivity and CXCR4 surface expression, rituximab induced upregulation of surface-expressed CXCR4, and growth-inhibitory effect of rituximab increased by plerixafor, supporting negative impact of CXCR4 on rituximab function. In conclusion, CXCR4 is a promising independent prognostic marker for R-CHOP-treated DLBCL patients, possibly due to inverse correlation between CXCR4 expression and rituximab sensitivity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Oncotarget
Año:
2019
Tipo del documento:
Article
País de afiliación:
Dinamarca