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- Junlen, HR, et al.
(författare)
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Absolute B cell counts in blood predict long-term response in follicular lymphoma patients treated with rituximab without chemotherapy
- 2020
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Ingår i: Annals of hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 99:10, s. 2357-2366
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Tidskriftsartikel (refereegranskat)abstract
- Rituximab monotherapy is widely used for follicular lymphoma. However, there are no established predictors for response or response duration. We analyzed the long-term prognostic relevance of pre-treatment absolute blood counts of lymphocytes with subsets and monocytes in 265 follicular lymphoma patients, uniformly treated with rituximab without chemotherapy, in two Nordic Lymphoma Group trials. There were 265 previously untreated, stage II–IV follicular lymphoma patients with a median follow-up of over 10 years. Absolute B cell counts ≥ median (0.09 × 109/L) were an independent predictor for shorter time to next treatment or death (multivariable analysis P = 0.010). In univariate analysis, absolute monocyte counts ≥ median (0.5 × 109/L) did not correlate with time to next treatment or death, but with inferior overall survival (P = 0.034). Absolute T cell or T cell subset counts were not predictive for outcome. High absolute B cell counts, possibly reflecting circulating lymphoma cells, have an unfavorable impact on time to next treatment or death in patients treated with rituximab without chemotherapy.
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- Merrien, M, et al.
(författare)
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2-Arachidonoylglycerol Modulates CXCL12-Mediated Chemotaxis in Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- To survive chemotherapy, lymphoma cells can relocate to protective niches where they receive support from the non-malignant cells. The biolipid 2-arachidonoylglycerol (2-AG), an agonist for the cannabinoid receptors CB1 and CB2, is released by stromal cells in the bone marrow. To investigate the role of 2-AG in lymphoma, we analyzed the chemotactic response of primary B-cell lymphoma cells enriched from peripheral blood of twenty-two chronic lymphocytic leukemia (CLL) and five mantle cell lymphoma (MCL) patients towards 2-AG alone and/or to the chemokine CXCL12. The expression of cannabinoid receptors was quantified using qPCR and the protein levels visualized by immunofluorescence and Western blot. Surface expression of CXCR4, the main cognate receptor to CXCL12, was analyzed by flow cytometry. Phosphorylation of key downstream signaling pathways activated by 2-AG and CXCL12 were measured by Western blot in three MCL cell lines and two primary CLL samples. We report that 2-AG induces chemotaxis in 80% of the primary samples, as well as 2/3 MCL cell lines. 2-AG induced in a dose-dependent manner, the migration of JeKo-1 cell line via CB1 and CB2. 2-AG affected the CXCL12-mediated chemotaxis without impacting the expression or internalization of CXCR4. We further show that 2-AG modulated p38 and p44/42 MAPK activation. Our results suggest that 2-AG has a previously unrecognized role in the mobilization of lymphoma cells by effecting the CXCL12-induced migration and the CXCR4 signaling pathways, however, with different effects in MCL compared to CLL.
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