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| 2. |
- Walsh, Sarah, et al.
(författare)
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Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia derives from an extensively hypermutated B cell that lacks ongoing somatic hypermutation
- 2005
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 29:7, s. 729-734
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoplasmacytic lymphoma (LPL) is a rare lymphoma thought to originate from a B cell stimulated to differentiate to a plasma cell, and which is usually accompanied by clonal IgM secretion, defining the diagnosis of Waldenström's macroglobulinemia (WM). However, the immunoglobulin variable heavy chain (VH) gene usage and the somatic hypermutation status have not been widely investigated in LPL. LPL biopsies (CD19+/CD20+/CD22+/CD5−/CD10−/CD23−/κ+) from 14 patients were included most of whom had a serum IgM component of variable magnitude (two cases with IgG). Highly mutated VH genes (mean mutation rate 8%) were revealed in 13 of 14 LPLs, whereas one case displayed a germline VH gene configuration. Cloning of the VH gene rearrangements in nine cases showed homogeneous sequences without intraclonal heterogeneity. Furthermore, no bias in the VH gene usage was shown, with VH3, VH4, and VH1 gene family members represented. These data confirm that the LPL precursor cell has been exposed to the germinal centre environment, as indicated by extensive hypermutation, but also that the transformation event occurred after affinity maturation, since there was a lack of intraclonal variation. Additionally, the VH gene repertoire was not skewed in LPL/WM as has been demonstrated in other B cell malignancies.
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- Abdulla, Maysaa, et al.
(författare)
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Expression of IDO1 and PD-L2 in Patients with Benign Lymphadenopathies and Association with Autoimmune Diseases
- 2023
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- The expression patterns of IDO1 and PD-L2 have not been thoroughly investigated in benign lymphadenopathies. The aim with this study was to elucidate how IDO1 and PD-L2 are expressed in benign lymphadenopathies in patients with autoimmune diseases (AD) compared to patients without AD. Formalin-fixed paraffin-embedded lymph nodes from 22 patients with AD and 57 patients without AD were immunohistochemically stained to detect IDO1 and PD-L2. The material was previously stained with EBER in situ hybridization to detect cells harboring the Epstein-Barr virus (EBV). IDO1 and PD-L2 were generally expressed by leukocytes to low degrees, while follicular IDO1+ cells were very rare. IDO1+ cells in single germinal centers were detected in five patients, and there was a high co-occurrence of follicular EBV+ cells in these cases (three of five patients). There were also significant correlations between interfollicular EBV+ cells and interfollicular IDO1+ cells (Spearman rho = 0.32, p = 0.004) and follicular IDO1+ cells (Spearman rho = 0.34, p = 0.004). High or low amounts of IDO1+ or PD-L2+ cells were not statistically significantly associated with patients with AD. However, the lymphadenopathy with the highest amount of interfollicular IDO1+ cells, which was also the only lymphadenopathy in which endothelial cells expressed IDO1, was in a patient with sarcoidosis. This study further supports that the EBV induces the expression of IDO1 and our findings should be recognized by future studies on IDO1 and PD-L2 in inflammatory and malignant conditions.
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| 5. |
- Abdulla, Maysaa, et al.
(författare)
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PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:4, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProgrammed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2, as well as Indoleamine 2,3-deoxygenase (IDO1) can be expressed both by tumor and microenvironmental cells and are crucial for tumor immune escape. We aimed to evaluate the role of PD-1, its ligands and IDO1 in a cohort of patients with primary diffuse large B-cell lymphoma of the CNS (PCNSL).Material and methodsTissue microarrays (TMAs) were constructed in 45 PCNSL cases. RNA extraction from whole tissue sections and RNA sequencing were successfully performed in 33 cases. Immunohistochemical stainings for PD-1, PD-L1/paired box protein 5 (PAX-5), PD-L2/PAX-5 and IDO1, and Epstein-Barr virus encoding RNA (EBER) in situ hybridization were analyzed.ResultsHigh proportions of PD-L1 and PD-L2 positive tumor cells were observed in 11% and 9% of cases, respectively. High proportions of PD-L1 and PD-L2 positive leukocytes were observed in 55% and 51% of cases, respectively. RNA sequencing revealed that gene expression of IDO1 was high in patients with high proportion of PD-L1 positive leukocytes (p = .01). Protein expression of IDO1 in leukocytes was detected in 14/45 cases, in 79% of these cases a high proportion of PD-L1 positive leukocytes was observed. Gene expression of IDO1 was high in EBER-positive cases (p = .0009) and protein expression of IDO1 was detected in five of six EBER-positive cases.ConclusionOur study shows a significant association between gene and protein expression of IDO1 and protein expression of PD-L1 in the tumor microenvironment of PCNSL, possibly of importance for prediction of response to immunotherapies.
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| 7. |
- Albertsson-Lindblad, Alexandra, et al.
(författare)
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Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:14, s. 1814-1820
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Tidskriftsartikel (refereegranskat)abstract
- For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.
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| 8. |
- Albertsson-Lindblad, Alexandra, et al.
(författare)
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Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 128:14, s. 1814-1820
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Tidskriftsartikel (refereegranskat)abstract
- For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untreated MCL, stage II-IV were eligible for inclusion. Primary endpoints were maximally tolerable dose (MTD) of LEN, and progression-free survival (PFS). Patients received six cycles q4w of L-B-R (L D1-14, B 90 mg/m(2) iv D1-2 and R 375 mg/m(2) iv D1) followed by single LEN (D1-21, q4w, cycles 7-13). 51 patients (median age 71 years) were enrolled 2009-2013. In phase I, the MTD of LEN was defined as 10 mg in cycles 2-6, and omitted in cycle 1. After six cycles, the complete remission rate (CRR) was 64% and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3 year overall survival was 73%. Infection was the most common non-hematological grade 3-5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in three patients; 2 PCP and 1 CMV retinitis. Second primary malignancies (SPM) were observed in eight patients (16%). LEN could safely be combined with R-B, when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs which may limit its use. http://clinicaltrials.gov: NCT00963534.
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| 9. |
- Alderborn, Anders, et al.
(författare)
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Genetically modified plants for non-food or non-feed purposes : straightforward screening for their appearance in food and feed
- 2010
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 48:2, s. 453-464
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Tidskriftsartikel (refereegranskat)abstract
- Genetically modified (GM) plants aimed at producing food/feed are part of regular agriculture in many areas of the World. Commodity plants have also found application as bioreactors, designated non-food/non-feed GM (NFGM) plants, thereby making raw material for further refinement to industrial, diagnostic or pharmaceutical preparations. Many among them may pose health challenge to consumers or livestock animals, if occurring in food/feed. NFGM plants are typically released into the environment, but are grown under special oversight and any among several containment practices, none of which provide full protection against accidental dispersal. Adventitious admixture with food or feed can occur either through distributional mismanagement or as a consequence of gene flow to plant relatives. To facilitate NFGM surveillance we propose a new mandatory tagging of essentially all such plants, prior to cultivation or marketing in the European Union. The suggested tag--Plant-Made Industrial or Pharmaceutical Products Tag (PMIP-T)--is envisaged to occur as a transgenic silent DNA identifier in host plants and designed to enable technically simple identification and characterisation of any NFGM. Implementation of PMIP-T would permit inexpensive, reliable and high-throughput screening for NFGM specifically. The paper outlines key NFGM prospects and challenges as well as the PMIP-T concept.
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