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  • 1.
    Adde, Magdalena
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Hagberg, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sundström, Christer
    Institutionen för genetik och patologi.
    Laurell, Anna
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Outcome for young high-risk aggressive B-cell lymphoma patients treated with CHOEP-14 and rituximab (R-CHOEP-14).2006Inngår i: Med Oncol, ISSN 1357-0560, Vol. 23, nr 2, s. 283-93Artikkel i tidsskrift (Fagfellevurdert)
  • 2.
    Amini, Rose-Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    von Heideman, Anne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Lagercrantz, Svetlana
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Bergh, Jonas
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    A novel B-cell line (U-2932) established from a patient with a diffuse large B-cell lymphoma following Hodgkin lymphoma2002Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 43, nr 11, s. 2179-2189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Little is known about mechanisms leading to secondary non-Hodgkin lymphomas (NHL) in patients treated for Hodgkin lymphoma (HL). Our aim was to characterise in detail a cell line derived from a diffuse large B-cell lymphoma (DLBCL) that had developed in a patient with relapsing HL. The cell line U-2932 was established from ascites in a patient suffering from DLBCL previously treated for HL with multiple chemotherapy regimens. Characterisation was based on morphology, immunophenotype, Epstein-Barr virus (EBV)-status, IgH gene rearrangement status, tumourigenicity, p53 sequencing, and immunohistochemical expression of p53, BCL-2 and BCL-6. The karyotype was investigated using G-banding, comparative genomic hybridisation (CGH) and spectral karyotype (SKY) analysis. This cell line shows typical morphological features of a DLBCL and grows as colonies in nude mice. It expresses a B-cell phenotype with a somatically hypermutated V(H)4-39 gene and is negative for EBV. The origin of U-2932 was confirmed by demonstrating an identical V(H)4 rearrangement in ascites from the patient. A point mutation of the tumour-suppressor gene p53 was detected in amino acid position 176 and immunohistochemical over-expression of the p53 protein was also demonstrated. U-2932 carries a complex karyotype including high-level amplifications of the chromosomal bands 18q21 and 3q27 and expresses aberrant BCL-2 and BCL-6 immunohistochemically. We were unable to investigate the clonal relationship between the original HL and U-2932. In conclusion, U-2932 is a unique B cell line established from a patient suffering from HL followed by NHL. Overexpression of BCL-2, BCL-6 and p53 may play a role in the tumourigenesis and drug resistance. This cell line may become a useful tool to better understand the mechanisms responsible for development of secondary NHL in patients treated for HL.

  • 3.
    Amini, Rose-Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Engström, Peter
    Christensson, Birger
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Relapsed Hodgkin's lymphoma: immunostaining patterns in relation to survival2002Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 43, nr 6, s. 1253-1260Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with relapsing Hodgkin's lymphoma (HL) have a rather poor prognosis and mechanisms that lead to resistance to therapy are poorly understood. Our aims were to investigate the immunohistochemical staining patterns of Rb (retinoblastoma protein) and the p53 tumour suppressor protein in HL at initial presentation and at relapse in order to elucidate a possible role in disease progression and resistance to therapy. Further to evaluate the presence and prognostic importance of Epstein-Barr virus (EBV) and anaplastic lymphoma kinase (ALK). Eighty-one cases of relapsing HL were reexamined histopathologically and immunostained for the expression of p53, Rb, ALK and CD30. EBV was detected with LMP-1 stainings and in situ hybridisation for EBER. Clinical data were extracted from the Swedish National Health Care Programme for HL. Median follow-up time was six years (range 0-12) from the date of relapse. The majority of cases were positive for p53 and Rb both at presentation and at relapse, though to a different extent. Both an increase and a decrease in the proportion of stained tumour cells were observed. None of our cases was ALK-positive and 44% were EBV-positive. No specific staining pattern was directly correlated to survival. In 12 patients a switch in HL subtype from diagnosis to relapse was observed and the five-year Hodgkin-specific survival (HLS) was statistically significantly inferior, 37 vs 81% (p = 0.002), in those patients. We found a significant relation between the expression of p53 and EBV at diagnosis and relapse, indicating a clonal relationship. We were unable to find any specific staining pattern of p53 or Rb, affecting survival.

  • 4.
    Amini, Rose-Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för patologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients1997Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 71, nr 4, s. 510-516Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immunohistochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma.

  • 5.
    Amini, Rose-Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    [Core needle biopsies for lymphoma diagnosis seriously affect diagnostics, treatment development and research].2017Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, artikkel-id EMDHArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Core needle biopsies for lymphoma diagnosis seriously affect diagnostics, treatment development and research Core needle biopsies (CNBs) are widely used in clinical diagnostic labs to aid in the diagnosis of malignant lymphomas and in latter years their use is increasing. CNBs provide a rapid method for obtaining tumour material and may be beneficial when the affected lymph nodes are located deep in the abdominal cavity or mediastinum and surgical excisional biopsies may be difficult to perform. However, according to the Swedish Haematopathology Quality and Standardization Committee, CNBs are insufficient for lymphoma diagnostic purposes and the guidelines state that material from surgical excisional biopsies are mandatory in order to obtain a robust histopathological evaluation of the lymph node architecture, cellular composition and growth pattern. Surgical excision biopsies also ensure that adequate material is available if additional molecular analyses should be required and also to facilitate future research.

  • 6. Andréasson, Ulrika
    et al.
    Dictor, Michael
    Jerkeman, Mats
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Linderoth, Johan
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Borrebaeck, Carl A K
    Ek, Sara
    Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells2009Inngår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 84, nr 12, s. 803-808Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified for predictive or early diagnosis. Gene expression analyses have identified genes changing on transformation but have failed to be reproducible in different studies, reflecting the heterogeneity within the tumor tissue and between tumor samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays were performed, using flow cytometry sorted tumor cells derived from FL and transformed DLBCL. To identify molecular targets associated with the transformation, subsequent immunohistochemistry (IHC) analyses of the corresponding proteins were performed. Using highly purified cells, this study identified 163 genes, which were significantly deregulated during the transformation in a majority of cases. Among the upregulated transcripts, 13 genes were selected for validation using IHC, based on the availability of commercial antibodies, and galectin-3 and NEK2 proteins specifically identify DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells through cell sorting, thereby reducing the heterogeneity due to infiltrating cells, it was possible to identify distinct differences between tumor entities rather than variations due to cellular composition. Galectin-3 and NEK2 both identified a subgroup of DLBCL-tr, and the function of these protein markers also suggests a biological role in the transformation process.

  • 7. Arne, Kolstad
    et al.
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Jerkeman, Mats
    Gronbaek, Kirsten
    Elonen, Erkki
    Raty, Riikka
    Pedersen, Lone Bredo
    Loft, Annika
    Bogsrud, Trond Velde
    Nordstrom, Marie
    Hansen, Per Boye
    Fagerli, Unn-Merete
    Nilsson-Ehle, Herman
    Lauritzsen, Grete Fossum
    Lehmann, Anne Kristine
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Karjalainen-Lindsberg, Marja-Liisa
    Ralfkiaer, Elisabeth
    Ehinger, Mats
    Delabie, Jan
    Bentzen, Hans
    Schildt, Jukka
    Kostova-Aherdan, Kamelia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Frederiksen, Henrik
    Brown, Peter de Nully
    Geisler, Christian H.
    Nordic MCL3 Study: Zevalin Combined with High-Dose Chemotherapy Followed by Autologous Stem Cell Support As Late Intensification for Mantle Cell Lymphoma (MCL) Patients < 66 Years Not in CR After Induction Chemoimmunotherapy: No Benefit of Zevalin2012Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, nr 21, s. 747-Artikkel i tidsskrift (Fagfellevurdert)
  • 8. Askling, J
    et al.
    Fored, C M
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Brandt, L
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Ekbom, A
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Molekylär och morfologisk patologi.
    Bertilsson, L
    Cöster, L
    Geborek, P
    Jacobsson, L T
    Lindblad, S
    Lysholm, J
    Rantapää-Dahlqvist, S
    Saxne, T
    Klareskog, L
    Feltelius, N
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists2005Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, nr 10, s. 1414-1420Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear.

    OBJECTIVE:

    To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA.

    METHODS:

    A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed.

    RESULTS:

    Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas.

    CONCLUSION:

    Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

  • 9.
    Baecklund, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Iliadou, Anastasia
    Granath, Fredrik
    Ekbom, Anders
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Feltelius, Nils
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Klareskog, Lars
    Askling, Johan
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis2006Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 54, nr 12, s. 3774-3781Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes.

    METHODS:

    We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters.

    RESULTS:

    We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores.

    CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.

  • 10.
    Baecklund, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Hellgren, K.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Askling, J.
    Does Biological Therapy Alter the Lymphoma Risk or Distribution of Lymphoma Subtypes in Patients with ra?2013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr Suppl. 3, s. 427-427Artikkel i tidsskrift (Annet vitenskapelig)
  • 11.
    Baecklund, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Iliadou, Anastasia
    Askling, Johan
    Ekbom, Anders
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Granath, Fredrik
    Catrina, Anca Irinel
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Feltelius, Nils
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Klareskog, Lars
    Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis2006Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 54, nr 3, s. 692-701Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.

    METHODS:

    We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.

    RESULTS:

    The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.

    CONCLUSION:

    Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.

  • 12.
    Baecklund, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Natkunam, Yasodha
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Iliadou, Anastasia
    Askling, Johan
    Ekbom, Anders
    Feltelius, Nils
    Klareskog, Lars
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Lossos, Izidore S.
    Levy, Ronald
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Expression of the human germinal-centre-associated lymphoma protein in diffuse large B-cell lymphomas in patients with rheumatoid arthritis2008Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 141, nr 1, s. 69-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse large B-cell lymphomas (DLBCL) can be subdivided into germinal centre (GC)-like and non-GC-like subtypes by CD10, BCL6 and MUM1/IRF4 status. We previously reported that patients with severe rheumatoid arthritis (RA) are at increased risk of non-GC DLBCL. This study examined a new GC-marker, human germinal-centre-associated lymphoma (HGAL) protein, in RA-DLBCL. Of 111, 38 (34%) DLBCL were HGAL-positive and showed less disseminated disease and a tendency toward improved overall survival compared to HGAL-negative cases. This supports that a majority of RA-DLBCL are of non-GC origin, indicating a specific role for activated peripheral B cells in the pathogenesis of RA-DLBCL.

  • 13.
    Berglund, Ake
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Nygren, Peter
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Hagberg, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Pahlman, Lars
    Institutionen för kirurgiska vetenskaper. Gastrointestinal Surgery.
    Sundin, Anders
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sundström, Christer
    Institutionen för genetik och patologi.
    [Limit investigation in cancer of unknown primary site]2005Inngår i: Lakartidningen, ISSN 0023-7205, Vol. 102, nr 41, s. 2946-8, 2950Artikkel i tidsskrift (Annet vitenskapelig)
  • 14.
    Berglund, Mattias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Roos, Göran
    Erlanson, Martin
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Larsson, Catharina
    Lagercrantz, Svetlana
    Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma2007Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 20, nr 1, s. 63-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Follicular lymphoma is commonly transformed to a more aggressive diffuse large B-cell lymphoma (DLBCL). In order to molecularely characterize this histiological and clinical transformation, comparative genomic hybridization was applied on 23 follicular lymphoma and 35 transformed DLBCL tumors from a total of 30 patients. The results were also compared with our published findings in de novo DLBCL. Copy number changes were detected in 70% of follicular lymphoma and in 97% of transformed DLBCL. In follicular lymphoma, the most common alterations were +18q21 (33%), +Xq25–26 (28%), +1q31–32 (23%), and -17p (23%), whereas transformed DLBCL most frequently exhibited +Xq25–26 (36%), +12q15 (29%), +7pter-q22 (25%), +8q21 (21%), and -6q16–21(25%). Transformed DLBCL showed significantly more alterations as compared to follicular lymphoma (P=0.0001), and the alterations -6q16–21 and +7pter-q22 were only found in transformed DLBCL but not in follicular lymphoma (P=0.02). Alterations involving +13q22 were significantly less frequent, whereas -4q13–21 was more common in transformed as compared to de novo DLBCL (P=0.01 and P=0.02, respectively). Clinical progression from follicular lymphoma to transformed DLBCL is on the genetic level associated with acquirement of increasing number of genomic copy number changes, with non-random involvement of specific target regions. The findings support diverse genetic background between transformed and de novo DLBCL.

  • 15.
    Berglund, Mattias
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Thunberg, Ulf
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Amini, Rose-Marie
    Institutionen för genetik och patologi.
    Book, Majlis
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Roos, Göran
    Erlanson, Martin
    Linderoth, Johan
    Dictor, Michael
    Jerkeman, Mats
    Cavallin-Ståhl, Eva
    Sundström, Christer
    Institutionen för genetik och patologi.
    Rehn-Eriksson, Suzanne
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Backlin, Carin
    Institutionen för genetik och patologi.
    Hagberg, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Rosenquist, Richard
    Institutionen för genetik och patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis.2005Inngår i: Mod Pathol, ISSN 0893-3952, Vol. 18, nr 8, s. 1113-20Artikkel i tidsskrift (Annet vitenskapelig)
  • 16.
    Blom, T
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Nilsson, G
    Institutionen för genetik och patologi.
    Sundström, C
    Institutionen för genetik och patologi.
    Nilsson, K
    Institutionen för genetik och patologi.
    Hellman, L
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Characterization of a human basophil-like cell line (LAMA-84)1996Inngår i: Scand. J. Immunol., Vol. 44, s. 54-61Artikkel i tidsskrift (Fagfellevurdert)
  • 17. Borssen, Magnus
    et al.
    Cullman, Inger
    Noren-Nystrom, Ulrika
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Porwit, Anna
    Forestier, Erik
    Roos, Göran
    hTERT promoter methylation and telomere length in childhood acute lymphoblastic leukemia: associations with immunophenotype and cytogenetic subgroup2011Inngår i: Experimental Hematology, ISSN 0301-472X, E-ISSN 1873-2399, Vol. 39, nr 12, s. 1144-1151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Telomere maintenance, important for long-term cell survival and malignant transformation, is directed by a multitude of factors, including epigenetic mechanisms, and has been implicated in outcomes for patients with leukemia. In the present study, the objective was to investigate the biological and clinical significance of telomere length and promoter methylation of the human telomerase reverse transcriptase gene in childhood acute lymphoblastic leukemia. A cohort of 169 childhood acute lymphoblastic leukemias was investigated for telomere length, human telomerase reverse transcriptase gene promoter methylation status, genomic aberrations, immunophenotype, and clinical outcomes. Methylation of the core promoter of the human telomerase reverse transcriptase (hTERT) gene was demonstrated in 24% of diagnostic samples, with a significant difference between B-cell precursor (n = 130) and T-cell acute lymphoblastic leukemia (ALL) (n = 17) cases (18% and 72%, respectively; p < 0.001). No remission sample demonstrated hTERT promoter methylation (n = 40). Within the B-cell precursor group, t(12;21)(p13;q22) [ETV6/RUNX1] cases (n = 19) showed a much higher frequency of hTERT methylation than high-hyperdiploid (51 61 chromosomes) ALL (n = 44) (63% and 7%, respectively; p < 0.001). hTERT messenger RNA levels were negatively associated with methylation status and, in the t(12;21) group, methylated cases had shorter telomeres (p = 0.017). In low-risk B-cell precursor patients (n = 101), long telomeres indicated a worse prognosis. The collected data from the present study indicate that the telomere biology in childhood ALL has clinical implications and reflects molecular differences between diverse ALL subgroups.

  • 18.
    Boström, Hans
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Leuchowius, Karl-Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Hallböök, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Nordgren, Ann
    Thörn, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Thorselius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Söderberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    U-2973, a novel B-cell line established from a patient with a mature B-cell leukemia displaying concurrent t(14;18) and MYC translocation to a non-IG gene partner2008Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 81, nr 3, s. 218-225Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    B-cell lymphomas/leukemias with simultaneous t(14;18)(q32;q21) and MYC rearrangements have recently been shown to constitute a separate diagnostic entity, presenting with a rapid clinical course and a very poor prognosis. We describe the establishment of an Epstein-Barr virus negative cell line, designated U-2973, from a male patient with a de novo aggressive B-cell lymphoma/leukemia and very high peripheral blast cell count. Flow cytometry of bone marrow cells and U-2973 displayed a mature B-cell phenotype, and immunostaining showed expression of MYC and BCL2. IG gene rearrangement data were consistent with a lymphoid neoplasm of germinal centre derivation. Cytogenetic studies using conventional G-banding, fluorescent in situ hybridization, spectral karyotyping and single nucleotide polymorphism array demonstrated a complex karyotype with both a t(14;18) and double translocations between MYC and a non-IG gene partner located at chromosome 12p12.1.

  • 19. Brauner, Susanna
    et al.
    Zhou, Wei
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Green, Tina M.
    Young, Ken He
    Lofstrom, Bjorn
    Lundberg, Ingrid
    Pedersen, Lars Moller
    Moller, Michael Boe
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Baecklund, Eva
    Wahren-Herlenius, Marie
    Ro52 Expression is a Prognostic Factor for Survival in B Cell Lymphoma2013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr S1, s. A40-A40Artikkel i tidsskrift (Annet vitenskapelig)
  • 20. Buckley, Patrick G.
    et al.
    Walsh, Sarah H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Roos, Göran
    Langford, Cordelia F.
    Dumanski, Jan P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Genome-wide microarray-based comparative genomic hybridization analysis of lymphoplasmacytic lymphomas reveals heterogeneous aberrations2009Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 50, nr 9, s. 1528-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lymphoplasmacytic lymphoma (LPL) is not a sharply delineated lymphoma entity, either morphologically, phenotypically, or clinically. The diagnosis is often made by excluding other small cell lymphomas with plasmacytic differentiation, thus a genetic diagnostic marker would be of great benefit. Conventional cytogenetic techniques have previously demonstrated a deletion of 6q in a proportion of cases, varying from 7 to 55%. In this report, we apply array-based comparative genomic hybridization on 11 LPL samples. Genomic aberrations were detected in 9 of 11 cases, and included gains and losses. In general, the number of genetic aberrations was relatively low (two to three abnormalities per case). Recurrent aberrations detected were deletion of 6q (two cases), deletion of chromosome 17 (two cases), gain of 3q (two cases), and gain of chromosome 7 (two cases). This report not only confirms the reported loss of 6q in a proportion of cases but also highlights the genetic heterogeneity of LPL, in accordance with the known immunophenotypical, morphological, and clinical diversity of the disease.

  • 21. Bäckman, Eva
    et al.
    Bergh, Ann-Charlotte
    Lagerdahl, Irena
    Rydberg, Björn
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Tobin, Gerard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Linderholm, Mats
    Rosén, Anders
    Thioredoxin, produced by stromal cells retrieved from the lymph node microenvironment, rescues chronic lymphocytic leukemia cells from apoptosis in vitro2007Inngår i: Haematologia, ISSN 0017-6559, E-ISSN 1568-5594, Vol. 92, nr 11, s. 1495-1504Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Objectives: The redox-regulatory protein thioredoxin has several functions including transcriptional regulation, and antioxidant, cytokine, and chemokine activities. We have previously shown that extracellular thioredoxin protects B-cell chronic lymphocytic leukemia (CLL) cells from apoptosis in vitro. In this study we were interested to determine whether thioredoxin is produced by cells surrounding the CLL cells in the in vivo microenvironment and whether this cell-derived thioredoxin has any leukemia growth-promoting effect in vitro. Design and Methods: Lymph nodes from CLL patients (n=25) were analyzed for thioredoxin expression by immunohistology. Stromal cells purified from the lymph nodes were analyzed for thioredoxin secretion at the single cell level using an ELIspot assay. The survival effect of the stromal-derived thioredoxin was tested by co-culturing stromal- and CLL cells with and without Fab-fragments of an anti-thioredoxin antibody. Results: The results indicated that the thioredoxin production correlated with the amount of proliferating cells and was mainly localized to the proliferation centers (pseudofollicles) in the CLL lymph nodes. The leukemia cells per se showed minimal thioredoxin levels; in contrast, stromal cells strongly expressed thioredoxin. Purified primary stromal cells, which secreted extracellular thioredoxin, significantly protected the CLL cells from undergoing apoptosis in 72 h co-cultures. Interestingly, this anti-apoptotic effect could be abrogated by addition of Fab-fragments of an anti- thioredoxin antibody. Interpretation and Conclusions: In conclusion, we have shown that stromal cells in the lymph node microenvironment produce thioredoxin and that the thioredoxin production is localized to the proliferation centers of the CLL lymph nodes. In addition, thioredoxin produced by purified stromal cells rescued CLL cells from apoptosis in vitro.

  • 22.
    Cahill, Nicola
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Bergh, A-C
    Kanduri, M
    Göransson-Kultima, H
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Mansouri, Larry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Isaksson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ryan, F
    Smedby, K E
    Juliusson, G
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Rosén, A
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments.2013Inngår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, nr 1, s. 150-158Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n=36) and patient-matched peripheral blood and lymph node samples (n=20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-β and NF-κB/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event.

  • 23. Canedo, P.
    et al.
    Thorsélius, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Sällström, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Rosén, A.
    Söderberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    A follicular dendritic cell line promotes somatic hypermutations in Ramos cells in vitro2009Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 69, nr 1, s. 70-71Artikkel i tidsskrift (Fagfellevurdert)
  • 24. Chang, Ellen T.
    et al.
    Smedby, Karin Ekström
    Hjalgrim, Henrik
    Schöllkopf, Claudia
    Porwit-MacDonald, Anna
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Tani, Edneia
    d'Amore, Francesco
    Melbye, Mads
    Adami, Hans-Olov
    Glimelius, Bengt
    Medication use and risk of non-Hodgkin's lymphoma2005Inngår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 162, nr 10, s. 965-974Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conflicting results from previous epidemiologic studies shed little light on whether medication use is associated with risk of non-Hodgkin's lymphoma (NHL). To investigate this question, the authors conducted a population-based case-control study in Denmark and Sweden from 1999 to 2002, including 3,055 incident NHL cases and 3,187 controls. Participants reported their past use of medications and history of particular medical conditions. Unconditional logistic regression was used to estimate multivariate odds ratios and 95% confidence intervals for the associations between medication use and risk of NHL; all statistical tests were two sided. Use of antibiotics more than 10 times during adulthood was positively associated with risk of NHL and most major NHL subtypes; when users were compared with nonusers, the odds ratio for NHL was 1.8 (95% confidence interval: 1.4, 2.3); p(trend) for total antibiotic use <0.001. In addition, high cumulative use of nonsteroidal anti-inflammatory drugs was marginally associated with elevated NHL risk. Other medications evaluated were not associated with risk of NHL or its most common subtypes. Findings suggest that inflammation, infections, susceptibility to infections, and/or use of antibiotics or nonsteroidal anti-inflammatory drugs to treat these conditions may increase the risk of NHL. However, most of the medications examined were not associated with NHL risk.

  • 25. Cuccuini, Wendy
    et al.
    Briere, Josette
    Mounier, Nicolas
    Voelker, Hans-Ullrich
    Rosenwald, Andreas
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Cogliatti, Sergio
    Hirchaud, Edouard
    Ysebaert, Loic
    Bron, Dominique
    Soulier, Jean
    Gaulard, Philippe
    Houlgatte, Remi
    Gisselbrecht, Christian
    Thieblemont, Catherine
    MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation2012Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 119, nr 20, s. 4619-4624Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Approximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC+). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by highdose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC+ rearrangement, targeted as either simple hit (25%) or complex hits (n = 75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and re