scholarly journals High CXCR4 expression impairs rituximab response and the prognosis of R-CHOP-treated diffuse large B-cell lymphoma patients

Oncotarget ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 717-731 ◽  
Author(s):  
Maria Bach Laursen ◽  
Linn Reinholdt ◽  
Anna Amanda Schönherz ◽  
Hanne Due ◽  
Ditte Starberg Jespersen ◽  
...  
2014 ◽  
Vol 235 (3) ◽  
pp. 445-455 ◽  
Author(s):  
María José Moreno ◽  
Rosa Bosch ◽  
Rebeca Dieguez-Gonzalez ◽  
Silvana Novelli ◽  
Ana Mozos ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Rasha Haggag ◽  
Naglaa A. Mostafa ◽  
Marwa Nabil ◽  
Hala A. Shokralla ◽  
Neveen F. H. Sidhom

Background: The aim of this study was to investigate the prognostic role of mammalian target of Rapamycin (mTOR) and C-X-C chemokine receptor type 4 (CXCR4) in diffuse large-B-cell lymphoma (DLBCL) patients.Patients and methods: This retrospective study was collected data from 64 de novo DLBCL patients, who received standardized R-CHOP therapy at two oncology centers. CXCR4 and mTOR expressions were assessed by immunohistochemistry.Results: Out of the 64 DLBCL patients, 40 patients were positive for CXCR4 (62.5%) and 35 patients for mTOR (54.7%) expressions. CXCR4 expression was positively correlated with mTOR expression (r = 0.7; p < .001). While mTOR expression was significantly associated with high lactate dehydrogenase level (p = .03) and number of extranodal sites one or more (p =.02), CXCR4 expression was significantly associated with high IPI score (p < .001) and ECOG PS (p = .005). Furthermore, theexpression levels of mTOR and CXCR4 were significantly associated with older ages and poor response to treatment (p = .04, <.001 and .04, .03, respectively). After a median Follow up of 22 months, mean ± SD overall survival (OS) was 65.391 ± 4.705. Kaplan–Meier analysis showed that patients positive for mTOR and CXCR4 expression had shorter DFS (p = .01 & .02) and OS (p = .02 & .04). Multivariate analysis showed that CXCR4 and mTOR positivity is an independent prognostic factor for significantly poorer DFS (p = .03, and .02 respectively) but not for OS (p = .09 and .08 respectively) in the DLBCL pateints.Conclusion: Our results indicate that the expression of CXCR4 and mTOR may be poor prognostic biomarkers in DLBCL.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18533-e18533
Author(s):  
Byung Woog Kang ◽  
Jong Gwang Kim ◽  
Yee Soo Chae ◽  
Soo Jung Lee ◽  
Sang Kyun Sohn ◽  
...  

e18533 Background: This study investigated the activation of nuclear factor kB (NFkB) and the chemokine receptor CXCR4 co-expression in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. Methods: Seventy patients with DLBCL and treated with rituximab-CHOP (RCHOP) were included. Tissue microarray blocks were created from 70 cases of DLBCL. Sections were stained with antibodies to IKKα, p-IkB, p50, p52, and CXCR4. To classify cases of DLBCL into GCB (germinal center B-cell-like) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 has been used in this study. A numeric intensity score of 0-3 was assigned each case. Negative was scored if 0/+1 and positive was scored if 2+/3+. Results: The median age was 66.5 years (range, 17-87) and 58.6% were male. Twenty-seven patients (38.6%) had stage III and IV at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their IPI. The overall incidence of BM involvement was 5.7%. Positive expression for NFkB and CXCR4 were more than 80%. In NFkB and CXCR4 status, there are no significant difference between GCB and non-GCB. High NFkB expression is associated with CXCR4 expression and they are co-expressed in about two thirds of patients. With a median follow-up duration of 28.7 months (range, 0.1-76.1), the 5-year overall survival (OS) and event-free survival (EFS) rate was 67.4% and 79.8%, respectively. Neither NFkB nor CXCR4 were associated with DLBCL outcomes. Conclusions: In concolusion, none of the NFkB and CXCR4 expression profiles investigated in this study was found to be an independent prognostic marker for Korean patients with DLBCL. However, further studies on a larger scale are warranted to clarify the role of NFkB and CXCR4 as a prognostic marker.


Praxis ◽  
2016 ◽  
Vol 105 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Andreas Lohri

Zusammenfassung. Maligne Lymphome unterteilen sich zwar in über 60 Entitäten, das grosszellige B-Zell-Lymphom, das follikuläre Lymphom, der Hodgkin und das Mantelzell-Lymphom machen aber mehr als die Hälfte aller Lymphome aus. Im revidierten Ann Arbor staging system gelten die Suffixe «A» und «B» nur noch für den Hodgkin. «E» erscheint nur noch bei Stadien I und II. Eine Knochenmarksuntersuchung wird beim Hodgkin nicht mehr verlangt, beim DLBCL (Diffuse large B cell lymphoma) nur, falls das PET keinen Knochenmark-Befall zeigt. Der PET-Untersuchung, speziell dem Interim-PET, kommt eine entscheidende Bedeutung zu. PET-gesteuerte Therapien führen zu weniger Toxizität. Gezielt wirkende Medikamente mit eindrücklicher Wirksamkeit wurden neu zugelassen. Deren Kosten sind hoch. Eine strahlen- und chemotherapiefreie Behandlung maligner Lymphome wird in Zukunft möglich sein.


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