Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway / 中华医学杂志(英文版)

BACKGROUND@#Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.@*METHODS@#The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.@*RESULTS@#We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo .@*CONCLUSION@#Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Current situation and requirements of quality control of blood disease laboratory in Chongqing:a cross sectional study / 重庆医学

Objective To understand the current situation and requirements of laboratory quality control of blood diseases in Chongqing .Methods A self‐designed questionnaire was designed ,and the investigation was carried out in 60 hospitals of Chongqing district .The main contents of the investigation were related to the instruments of work environment ,the regulations ,the conditions of the personnel ,etc .Results A total of 60 questionnaires were distributed ,57 questionnaires were valid .In the study ,only 14 .04%laboratories were the blood disease specialist laboratory ,most hospitals could complete the basic inspection items .66 .67% hospitals had all the experimental procedures and SOP documents .Most of staffs were with intermediate professional titles and undergraduate education .A total of 35 .08% experimental equipments with the value of over 5 million RMB ,45 .61% equipments had a special in‐spection records .About 45 .61% test reports would refer to the clinical performance ,and had a strict signing guideline .Most of the research objects reflected the problems ,including the backward equipments and the lack of personnel ,and hoped to set up telemedi‐cine indemnity system and carry out further education .Conclusion The overall quality of the laboratory for blood diseases in Chongqing is better ,it is recommended to strengthen the full quality control ,to establish emergency system ,and to improve the quality and level of laboratory .