Signe Spetalen

• Tjønnfjord, Geir Erland; Osnes, Liv Toril N.; Spetalen, Signe; Haave, Ulla; Popperud, Trine Haug & Maniaol, Angelina H. [Show all 17 contributors for this article] (2026). Anti‐MAG Polyneuropathy: Characterization of the Monoclonal Gammopathy and Clonal B‐Cell Population. Journal of Immunology Research. ISSN 2314-8861. 2026(1), p. 1–9. doi: 10.1155/jimr/1959235. Full text in Research Archive Show summary

  Polyneuropathy due to antibodies to myelin‐associated glycoprotein (MAG) is a rare disease with an estimated prevalence of 1 per 100,000. Symptoms start in the sixth or seventh decade of life, presenting sensory polyneuropathy with sensory ataxia, paresthesia, mild motor deficit, and tremor of upper extremities. The neurophysiological features are compatible with length‐dependent demyelination. It is caused by monoclonal gammopathy of the IgM type produced by clonal B cells. In recent years the monoclonal anti‐CD20 antibody has become the preferred first‐line treatment, but with limited efficacy. We identified a cohort of 42 patients diagnosed with anti‐MAG polyneuropathy. Clinical data were collected retrospectively, and flow cytometry files and immune histochemistry slides were reassessed. We report that in most cases of anti‐MAG polyneuropathy, the monoclonal IgM is kappa‐restricted, the B‐cell population shows lymphoplasmacytic differentiation, MYD88 L265P mutation is a frequent finding, and the clonal B‐cell population includes plasma cells. These findings most likely explain the low efficacy of rituximab monotherapy. We found the burden of symptoms to be high among patients with anti‐MAG polyneuropathy as most of our patients had received intravenous immunoglobulin infusions and/or B‐cell‐directed treatment. We suggest that future treatment protocols for anti‐MAG polyneuropathy should incorporate plasma cell‐directed drugs. Furthermore, we found complement receptor 1 (CD35) to be down regulated on clonal B lymphocytes but not on normal B lymphocytes in these patients. We suggest that this may be a common feature of clonal B lymphocytes in chronic lymphoproliferative diseases.

• Brunetti, Marta; Andersen, Kristin; Spetalen, Signe; Tjønnfjord, Geir Erland; Heim, Sverre & Micci, Francesca (2025). Cryptic Rearrangement of the KMT2A Gene in a B‐cell Acute Lymphoblastic Leukemia. Anticancer Research. ISSN 0250-7005. 45(3), p. 921–928. doi: 10.21873/anticanres.17479. Full text in Research Archive Show summary

  Background/Aim: A 30-year-old female diagnosed with B cell acute lymphoblastic leukemia (B-ALL) had a normal karyotype at diagnosis. Case Report: The case was investigated further by fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), and reverse-transcription polymerase chain reaction (RT-PCR) followed by Cycle sequencing. The diagnostic karyotype was normal (46,XX), but FISH studies on tumor cells using a KMT2A break-apart probes showed that the proximal part of KMT2A was inserted into an apparently normal chromosome 4 with concomitant loss of the distal part of the probe. aCGH identified losses within 11q23.3 and 4q21.3q22.1 with the breakpoints mapping inside the KMT2A and AFF1 loci. The presence of the putative KMT2A::AFF1 fusion gene was confirmed by FISH analysis and RT-PCR/Cycle sequencing; an in-frame fusion was detected between KMT2A (exon 9) and AFF1 (exon 6). The patient underwent allogenic stem cell transplantation and reached complete remission. Conclusion: This case highlights the need to supplement banding cytogenetics with appropriate molecular (cyto)genetic techniques whenever the karyotype does not reveal characteristic aberrations. Although KMT2A rearrangements in both lymphoblastic and myeloid acute leukemias usually arise through karyotypically visible chromosomal recombinations, this is not always the case.

• Ludvigsen, Lene Ugilt Pagter; Åsberg, Anders; Spetalen, Signe; Sørensen, Mia Dahl; Hamilton-Dutoit, Stephen & Gramkow, Ann-Maria [Show all 19 contributors for this article] (2025). Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark. American Journal of Transplantation. ISSN 1600-6135. 25(7), p. 1547–1560. doi: 10.1016/j.ajt.2025.01.035. Full text in Research Archive Show summary

  Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBVseronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.

• Fischer, Anja; Albert, Thomas K.; Moreno, Natalia; Interlandi, Marta; Mormann, Jana & Glaser, Selina [Show all 55 contributors for this article] (2024). Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas. Nature Communications. 15:8571(1), p. 1–18. doi: 10.1038/s41467-024-52826-0. Full text in Research Archive Show summary

  Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOSSMARCB1-, which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOSSMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOSSmarcb1-. In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOSSMARCB1- within the TME.

• Hamnvik, Lars Henrik; Tjønnfjord, Geir Erland; Spetalen, Signe & Dalgaard, Jakob (2024). Long-lasting severe anemia following treatment with natalizumab for relapsing–remitting multiple sclerosis: a case report. Journal of Medical Case Reports. 18(1). doi: 10.1186/s13256-024-04562-8. Full text in Research Archive Show summary

  Background Natalizumab is a monoclonal antibody used to treat patients with relapsing–remitting multiple sclerosis. Anemia is a recognized side effect, but it is usually mild and of a short duration when natalizumab is stopped. Here, we describe a case of a young woman with severe and especially long lasting anemia associated with treatment with natalizumab, persisting up to a year after treatment was stopped. Case presentation A 24 year-old Caucasian woman with relapsing–remitting multiple sclerosis developed severe transfusion dependent anemia after 27 infusions with natalizumab, which was her first and only treatment for her multiple sclerosis. Extensive hematologic diagnostics did not reveal any malignant cause or any other plausible non-malignant cause for her anemia. The bone marrow was found to be hypercellular, with a maturation arrest of the erythropoiesis and with grade 1–2 fibrosis. No specific treatment for the anemia was given. The hemoglobin level showed signs of spontaneous increase after nearly one year after natalizumab was discontinued. Conclusion Severe anemia can be caused by treatment with natalizumab. This case adds information to the few other similar reported cases, demonstrating the potential duration of the anemia, as well as detailed description of hematologic findings. The mechanism is most likely due to inhibition of α4 subunit of the α4β1-integrin, which is present on both lymphocytes and erythroid precursor cells.

• Brunetti, Marta; Andersen, Kristin; Spetalen, Signe; Lenartova, Andrea; Osnes, Liv T. N. & Vålerhaugen, Helen [Show all 8 contributors for this article] (2024). NUP214 fusion genes in acute leukemias: genetic characterization of rare cases. Frontiers in Oncology. 14:1371980, p. 1–8. doi: 10.3389/fonc.2024.1371980. Full text in Research Archive Show summary

  Introduction Alterations of the NUP214 gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/DEK::NUP214, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding. Methods We examined 9 cases of acute leukemia with NUP214 rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated. Results The chimeras DEK::NUP214, SET::NUP214, and NUP214::ABL1 were found, only the first of which can be readily detected by karyotyping. Discussion The identification of a specific NUP214 rearrangement is fundamental in the management of these patients, i.e., AMLs with DEK::NUP214 are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements.

• Brunetti, Marta; Andersen, Kristin; Trøen, Gunhild; Micci, Francesca; Spetalen, Signe & Lenartova, Andrea [Show all 8 contributors for this article] (2024). Molecular genetic characterization of myeloid neoplasms with idic(X)(q13) and i(X)(q10). Frontiers in Oncology. 14:1428984, p. 1–8. doi: 10.3389/fonc.2024.1428984. Full text in Research Archive Show summary

  Background/Aim: Isodicentric [idic(X)(q13)] and isochromosome [i(X)(q10)] are infrequent aberrations in neoplastic diseases. The former is mainly reported in elderly women with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), whereas the latter is mostly found as a secondary aberration or part of complex karyotypes in various types of neoplasms, including MDS and AML. Here, we present the molecular genetics and clinical features of six patients with myeloid neoplasia and the above-mentioned aberrations. Patients and Methods: Array comparative genome hybridization (aCGH) and next-generation sequencing (NGS) myeloid panel were used to examine genetic alterations in five bone marrow samples containing neoplastic cells carrying idic(X)(q13) and one sample with i(X)(q10). Results: The breakpoints of idic(X)(q13) were clustered within a 200 kbp region encompassing FAM236B, DMRTC1B, and DMRTC1. The breakpoint of i(X)(q10) was identified within a 112 kbp region on sub-band p11.22 containing SSX2, SSX2B, and SPANXN5. Pathogenic variants of TET2 were identified in four cases, SF3B1 in three cases, ASXL1 and SRSF2 in two cases each, whereas STAG2, RUNX1, U2AF1, and TP53 pathogenic variants were detected in only single cases. Conclusions: The breakpoints of idic(X)(q13) are within a 200kbp. i(X)(q10) in our study turned out to be a cryptic idic(X)(p11) aberration, reported for the first time here. TET2, SF3B1, ASXL1, or SRSF2 were highly prevalent in patients with idic(X)(q13)/i(X)(q10) abnormalities and were often associated with a worse prognosis.

• Sefland, Øystein; Gullaksen, Stein-Erik; Omsland, Maria; Reikvam, Håkon; Galteland, Eivind & Tran, Hoa Thi Tuyet [Show all 11 contributors for this article] (2024). Mass cytometric single cell immune profiles of peripheral blood from acute myeloid leukemia patients in complete remission with measurable residual disease. Cytometry Part B: Clinical Cytometry. ISSN 1552-4949. 106(6), p. 485–496. doi: 10.1002/cyto.b.22197. Full text in Research Archive Show summary

  Measurable residual disease (MRD) is detected in approximately a quarter of AML chemotherapy responders, serving as a predictor for relapse and shorter survival. Immunological control of residual disease is suggested to prevent relapse, but the mechanisms involved are not fully understood. We present a peripheral blood single cell immune profiling by mass cytometry using a 42-antibody panel with particular emphasis on markers of cellular immune response. Six healthy donors were compared with four AML patients with MRD (MRD+) in first complete remission (CR1MRD+). Three of four patients demonstrated a favorable genetic risk profile, while the fourth patient had an unfavorable risk profile (complex karyotype, TP53-mutation) and a high level of MRD. Unsupervised clustering using self-organizing maps and dimensional reduction analysis was performed for visualization and analysis of immune cell subsets. CD57+ natural killer (NK)-cell subsets were found to be less abundant in patients than in healthy donors. Both T and NK cells demonstrated elevated expression of activity and maturation markers (CD44, granzyme B, and phosho-STAT5 Y694) in patients. Although mass cytometry remains an expensive method with limited scalability, our data suggest the utility for employing a 42-plex profiling for cellular immune surveillance in whole blood, and possibly as a biomarker platform in future clinical trials. The findings encourage further investigations of single cell immune profiling in CR1MRD+ AML-patients.

• Nyquist, Emil; Dalgaard, Jakob; Spetalen, Signe; Torkildsen, Synne; Frøen, Hege & Galteland, Eivind [Show all 17 contributors for this article] (2023). Pathogenic DDX41 variants, possible response predictors to low-dose melphalan in hypo- and normocellular MDS and AML. British Journal of Haematology. ISSN 0007-1048. 204(2), p. 724–729. doi: 10.1111/bjh.19226. Full text in Research Archive
• Spasevska, Ivana; Sharma, Ankush; Steen, Chloe Beate; Josefsson, Sarah Elisabet; Blaker, Yngvild Nuvin & Kolstad, Arne [Show all 26 contributors for this article] (2023). Diversity of intratumoral regulatory T cells in B-cell non-Hodgkin lymphoma. Blood Advances. ISSN 2473-9529. 7(23), p. 7216–7230. doi: 10.1182/bloodadvances.2023010158. Full text in Research Archive Show summary

  Abstract Tumor-infiltrating regulatory T cells (Tregs) contribute to an immunosuppressive tumor microenvironment. Despite extensive studies, the prognostic impact of tumor-infiltrating Tregs in B-cell non-Hodgkin lymphomas (B-NHLs) remains unclear. Emerging studies suggest substantial heterogeneity in the phenotypes and suppressive capacities of Tregs, emphasizing the importance of understanding Treg diversity and the need for additional markers to identify highly suppressive Tregs. Here, we applied single-cell RNA sequencing and T-cell receptor sequencing combined with high-dimensional cytometry to decipher the heterogeneity of intratumoral Tregs in diffuse large B-cell lymphoma and follicular lymphoma (FL), compared with that in nonmalignant tonsillar tissue. We identified 3 distinct transcriptional states of Tregs: resting, activated, and unconventional LAG3+FOXP3− Tregs. Activated Tregs were enriched in B-NHL tumors, coexpressed several checkpoint receptors, and had stronger immunosuppressive activity compared with resting Tregs. In FL, activated Tregs were found in closer proximity to CD4+ and CD8+ T cells than other cell types. Furthermore, we used a computational approach to develop unique gene signature matrices, which were used to enumerate each Treg subset in cohorts with bulk gene expression data. In 2 independent FL cohorts, activated Tregs was the major subset, and high abundance was associated with adverse outcome. This study demonstrates that Tregs infiltrating B-NHL tumors are transcriptionally and functionally diverse. Highly immunosuppressive activated Tregs were enriched in tumor tissue but absent in the peripheral blood. Our data suggest that a deeper understanding of Treg heterogeneity in B-NHL could open new paths for rational drug design, facilitating selective targeting to improve antitumor immunity.

• Skånland, Sigrid S; Inngjerdingen, Marit; Bendiksen, Henrik; York, Jamie Piers; Spetalen, Signe & Munthe, Ludvig Andre [Show all 7 contributors for this article] (2022). Functional testing of relapsed chronic lymphocytic leukemia guides precision medicine and maps response and resistance mechanisms. An index case. Haematologica. ISSN 0390-6078. 107(8), p. 1994–1998. doi: 10.3324/haematol.2021.280393. Full text in Research Archive
• Jørgensen, Silje Fjellgård; Buechner, Jochen; Myhre, Anders Eivind; Galteland, Eivind; Spetalen, Signe & Kulseth, Mari Ann [Show all 19 contributors for this article] (2021). A Nationwide Study of GATA2 Deficiency in Norway-the Majority of Patients Have Undergone Allo-HSCT. Journal of Clinical Immunology. ISSN 0271-9142. doi: 10.1007/s10875-021-01189-y. Full text in Research Archive Show summary

  Purpose: GATA2 deficiency is a rare primary immunodeficiency that has become increasingly recognized due to improved molecular diagnostics and clinical awareness. The only cure for GATA2 deficiency is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The inconsistency of genotype-phenotype correlations makes the decision regarding "who and when" to transplant challenging. Despite considerable morbidity and mortality, the reported proportion of patients with GATA2 deficiency that has undergone allo-HSCT is low (~ 35%). The purpose of this study was to explore if detailed clinical, genetic, and bone marrow characteristics could predict end-point outcome, i.e., death and allo-HSCT. Methods: All medical genetics departments in Norway were contacted to identify GATA2 deficient individuals. Clinical information, genetic variants, treatment, and outcome were subsequently retrieved from the patients' medical records. Results: Between 2013 and 2020, we identified 10 index cases or probands, four additional symptomatic patients, and no asymptomatic patients with germline GATA2 variants. These patients had a diverse clinical phenotype dominated by cytopenia (13/14), myeloid neoplasia (10/14), warts (8/14), and hearing loss (7/14). No valid genotype-phenotype correlations were found in our data set, and the phenotypes varied also within families. We found that 11/14 patients (79%), with known GATA2 deficiency, had already undergone allo-HSCT. In addition, one patient is awaiting allo-HSCT. The indications to perform allo-HSCT were myeloid neoplasia, disseminated viral infection, severe obliterating bronchiolitis, and/or HPV-associated in situ carcinoma. Two patients died, 8 months and 7 years after allo-HSCT, respectively. Conclusion: Our main conclusion is that the majority of patients with symptomatic GATA2 deficiency will need allo-HSCT, and a close surveillance of these patients is important to find the "optimal window" for allo-HSCT. We advocate a more offensive approach to allo-HSCT than previously described.

• Kolstad, Arne; Illidge, Tim; Bolstad, Nils; Spetalen, Signe; Madsbu, Ulf Erik & Stokke, Caroline [Show all 19 contributors for this article] (2020). Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Advances. ISSN 2473-9529. 4(17), p. 4091–4101. doi: 10.1182/bloodadvances.2020002583. Full text in Research Archive Show summary

  For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20-based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the "cold" anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

• Munthe-Kaas, Monica Cheng; Forthun, Rakel Brendsdal; Brendehaug, Atle; Eek, Anette Kildal; Høysæter, Trude & Osnes, Liv T. N. [Show all 9 contributors for this article] (2020). Partial response to sorafenib in a child with a myeloid/lymphoid neoplasm, eosinophilia, and a ZMYM2-FLT3 fusion. Journal of Pediatric Hematology/Oncology. ISSN 1077-4114. 00:1890, p. 1–4. doi: 10.1097/MPH.0000000000001890. Full text in Research Archive Show summary

  Dysregulated tyrosine kinases in myeloid/lymphoid neoplasms with eosinophilia are rare, but do occur in children. To increase awareness of this diagnosis, we present a child who was diagnosed after a 3-year disease history. The patient was initially treated according to a T-cell lymphoblastic lymphoma protocol, but genetic analyses at recurrence revealed microdeletions resulting in an in-frame fusion of ZMYM2 and FLT3. Treatment with sorafenib, an FLT3 tyrosine kinase inhibitor, rapidly resulted in significant reduction of lymphadenopathy and normalization of white blood cell and eosinophil counts. At 17 months of treatment, he remains in complete hematological, but not molecular remission.

• Leppä, Sirpa; Jørgensen, Judit; Tierens, Anne; Meriranta, Leo; Østlie, Ingunn & Brown, Peter de Nully [Show all 23 contributors for this article] (2020). Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. Blood Advances. ISSN 2473-9529. 4(9), p. 1906–1915. doi: 10.1182/bloodadvances.2020001518. Full text in Research Archive Show summary

  Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We conducted a phase 2 trial in 139 patients aged 18 to 64 years who had primary DLBCL with an age-adjusted International Prognostic Index (aaIPI) score of 2 to 3 or site-specific risk factors for CNS recurrence. The goal was to assess whether a dose-dense immunochemotherapy with early systemic CNS prophylaxis improves the outcome and reduces the incidence of CNS events. Treatment consisted of 2 courses of high-dose methotrexate in combination with biweekly rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-14), followed by 4 courses of R-CHOP-14 with etoposide (R-CHOEP) and 1 course of high-dose cytarabine with R. In addition, liposomal cytarabine was administered intrathecally at courses 1, 3, and 5. Coprimary endpoints were failure-free survival and CNS progression rates. Thirty-six (26%) patients experienced treatment failure. Progression occurred in 23 (16%) patients, including three (2.2%) CNS events. At 5 years of median follow-up, failure-free survival, overall survival, and CNS progression rates were 74%, 83%, and 2.3%, respectively. Treatment reduced the risk of progression compared with our previous trial, in which systemic CNS prophylaxis was given after 6 courses of biweekly R-CHOEP (hazard ratio, 0.49; 95% CI, 0.31-0.77; P = .002) and overcame the adverse impact of an aaIPI score of 3 on survival. In addition, outcome of the patients with BCL2/MYC double-hit lymphomas was comparable to the patients without the rearrangements. The results are encouraging, with a low toxic death rate, low number of CNS events, and favorable survival rates. This trial was registered at www.clinicaltrials.gov as #NCT01325194.

• Torkildsen, Synne; Gorunova, Ludmila; Heim, Sverre; Tjønnfjord, Geir Erland; Spetalen, Signe & Risberg, Bente [Show all 8 contributors for this article] (2019). Molecular Genetic Characterization of Acute Myeloid Leukemia With Trisomy 4 as the Sole Chromosome Abnormality. Cancer Genomics & Proteomics. ISSN 1109-6535. 16(3), p. 175–178. doi: 10.21873/cgp.20123. Full text in Research Archive Show summary

  Background/Aim: The aim of the study was to determine the genetic and molecular consequences of trisomy 4, a recurrent but rare chromosomal abnormality in acute myeloid leukemia (AML). Materials and Methods: Interphase fluorescence in situ hybridization, reverse transcriptase-quantitative polymerase chain reaction for 28 chromosomal gene translocations/fusion genes, and targeted sequencing analyses were performed on five AMLs with trisomy 4 as the sole chromosomal anomaly. Results: An NPM1 frameshift mutation was found in all leukemic bone marrows, DNMT3A, FLT3, and IDH1 mutations were found in three, KIT and NRAS mutations in two, whereas IDH2 (R140Q), RUNX1, and WT1 mutations were found in only one patient each. The three patients with a DNMT3A (R882H) mutation have died. In contrast, the two patients whose leukemic cells were without this mutation, are alive 55 and 31 months after diagnosis, respectively. Conclusion: The results suggest a possible association between trisomy 4 and additional mutations that may influence prognosis.

• Nabel, Christopher S.; Sameroff, Stephen; Shilling, Dustin; Alapat, Daisy; Ruth, Jason R. & Kawano, Mitsuhiro [Show all 16 contributors for this article] (2019). Virome capture sequencing does not identify active viral infection in unicentric and idiopathic multicentric Castleman disease. PLOS ONE. 14:e0218660(6), p. 1–13. doi: 10.1371/journal.pone.0218660. Full text in Research Archive
• Habberstad, Andreas Hanssønn; Tran, Hoa Thi Tuyet; Randen, Ulla; Spetalen, Signe; Dybedal, Ingunn & Tjønnfjord, Geir Erland [Show all 7 contributors for this article] (2018). Neutropenia caused by hairy cell leukemia in a patient with myelofibrosis secondary to polycythemia vera: A case report. Journal of Medical Case Reports. 12(1). doi: 10.1186/s13256-018-1663-6. Full text in Research Archive Show summary

  Background Polycythemia vera is a myeloproliferative disease that sometimes evolves to myelofibrosis, causing splenomegaly and neutropenia. In this case report, we describe a patient with polycythemia vera and unexplained neutropenia who later turned out to also have hairy cell leukemia. Case presentation A middle-aged Caucasian man with polycythemia vera presented to our hospital with chronic mouth ulcers. Later he developed leukopenia and pancytopenia. Bone marrow biopsies showed fibrosis. Further morphological analyses of bone marrow and blood smears revealed probable transformation into acute myeloid leukemia. However, there were also cells indicating hairy cell leukemia. Morphological and immunohistochemical analyses later confirmed the presence of hairy cell leukemia in biopsies that had been present for 3 years. Treatment with cladribine temporarily reversed the patient’s neutropenia. Conclusions Hairy cell leukemia may mimic development to myelofibrosis in patients with polycythemia vera.

• Torkildsen, Synne; Brunetti, Marta; Gorunova, Ludmila; Spetalen, Signe; Beiske, Klaus & Heim, Sverre [Show all 7 contributors for this article] (2017). Rearrangement of the chromatin organizer special AT-rich binding protein 1 gene, SATB1, resulting from a t(3;5)(p24;q14) chromosomal translocation in acute myeloid leukemia. Anticancer Research. ISSN 0250-7005. 37(2), p. 693–698. doi: 10.21873/anticanres.11365. Full text in Research Archive
• Panagopoulos, Ioannis; Gorunova, Ludmila; Spetalen, Signe; Bassarova, Assia Vassileva; Beiske, Klaus & Micci, Francesca [Show all 7 contributors for this article] (2017). Fusion of the genes ataxin 2 like, ATXN2L, and Janus kinase 2, JAK2, in cutaneous CD4 positive T-cell lymphoma. OncoTarget. 8(61), p. 103775–103784. doi: 10.18632/oncotarget.21790. Full text in Research Archive
• Blaker, Yngvild Nuvin; Spetalen, Signe; Eide, Marianne Brodtkorb; Lingjærde, Ole Christian; Beiske, Klaus & Østenstad, Bjørn [Show all 13 contributors for this article] (2016). The tumour microenvironment influences survival and time to transformation in follicular lymphoma in the rituximab era. British Journal of Haematology. ISSN 0007-1048. 175(1), p. 102–114. doi: 10.1111/bjh.14201. Full text in Research Archive
• Panagopoulos, Ioannis; Gorunova, Ludmila; Kerndrup, Gitte; Spetalen, Signe; Tierens, Anne & Osnes, Liv T. N. [Show all 11 contributors for this article] (2016). Rare MLL-ELL fusion transcripts in childhood acute myeloid leukemia-association with young age and myeloid sarcomas? Experimental Hematology & Oncology. 5:8. doi: 10.1186/s40164-016-0037-2. Full text in Research Archive Show summary

  Background The chromosomal translocation t(11;19)(q23;p13) with a breakpoint within subband 19p13.1 is found mainly in acute myeloid leukemia (AML) and results in the MLL-ELL fusion gene. Variations in the structure of MLL-ELL seem to influence the leukemogenic potency of the fusion in vivo and may lie behind differences in clinical features. The number of cases reported so far is very limited and the addition of more information about MLL-ELL variants is essential if the possible clinical significance of rare fusions is to be determined. Case presentation Cytogenetic and molecular genetic analyses were done on the bone marrow cells of a 20-month-old boy with an unusual form of myelomonocytic AML with multiple myeloid sarcomas infiltrating bone and soft tissues. The G-banding analysis together with FISH yielded the karyotype 47,XY, +6,t(8;19;11)(q24;p13;q23). FISH analysis also demonstrated that MLL was split. RNA-sequencing showed that the translocation had generated an MLL-ELL chimera in which exon 9 of MLL (nt 4241 in sequence with accession number NM_005933.3) was fused to exon 6 of ELL (nt 817 in sequence with accession number NM_006532.3). RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcript. Conclusions Based on our findings and information on a few previously reported patients, we speculate that young age, myelomonoblastic AML, and the presence of extramedullary disease may be typical of children with rare MLL-ELL fusion transcripts.

• Fiskvik, Idun Hege; Beiske, Klaus; Delabie, Jan; Yri, Olav Erich; Spetalen, Signe & Karjalainen-Lindsberg, Marja-Liisa [Show all 10 contributors for this article] (2015). Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma. Leukemia and Lymphoma. ISSN 1042-8194. 56(6), p. 1742–1749. doi: 10.3109/10428194.2014.970550. Full text in Research Archive
• Bassarova, Assia Vassileva; Trøen, Gunhild; Spetalen, Signe; Micci, Francesca; Tierens, Anne & Delabie, Jan (2015). Lymphoplasmacytic lymphoma and marginal zone lymphoma in the bone marrow: Paratrabecular involvement as an important distinguishing feature. American Journal of Clinical Pathology. ISSN 0002-9173. 143(6), p. 797–806. doi: 10.1309/AJCP6ZODWV1CIDME. Full text in Research Archive Show summary

  Objectives: The differential diagnosis between bone marrow involvement by lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) is challenging because histology and immunophenotype of both diseases overlap. We revisited the diagnostic pathology features of both diseases in the bone marrow. Methods: We studied a series of bone marrow trephine biopsy specimens from 59 patients with Waldenström macroglobulinemia without extramedullary involvement and bone marrow biopsy specimens from 23 patients with well- characterized MZL who also had bone marrow involvement. H&E- and immunoperoxidase-stained sections of bone marrow trephine biopsy specimens as well as flow cytometry and classic cytogenetics performed on aspirations were reviewed. The study was complemented with MYD88 L265P mutation analysis of all samples. Results: The most distinguishing features of LPL with respect to MZL were focal paratrabecular involvement ( P < .001), the presence of lymphoplasmacytoid cells ( P < .001) and Dutcher bodies ( P < .001), increased numbers of mast cells ( P < .001), and the MYD88 L265P mutation ( P < .001). Conclusions: LPL can be reliably distinguished from MZL in the bone marrow by using a combination of pathology characteristics. Our findings stress the diagnostic importance of using the combination of the following parameters for a correct LPL diagnosis: paratrabecular infiltration, the presence of lymphoplasmacytoid cells and cells with Dutcher bodies, and an increased number of mast cells in addition to the presence of mutation.

• Midtvedt, Øyvind; Gran, Jan Tore; Solheim, Hanne; Kirkhus, Eva & Spetalen, Signe (2014). En mann i 40-årene med hevelse i begge øyehuler. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 134(15), p. 1472–1476. doi: 10.4045/tidsskr.13.0115. Full text in Research Archive
• Kleiveland, Charlotte Ramstad; Hult, Lene Therese Olsen; Spetalen, Signe; Kaldhusdal, Magne; Christoffersen, Trine Eker & Bengtsson, Oskar [Show all 9 contributors for this article] (2013). The Noncommensal Bacterium Methylococcus capsulatus (Bath) Ameliorates Dextran Sulfate (Sodium Salt)-Induced Ulcerative Colitis by Influencing Mechanisms Essential for Maintenance of the Colonic Barrier Function. Applied and Environmental Microbiology. ISSN 0099-2240. 79(1), p. 48–56. doi: 10.1128/AEM.02464-12. Full text in Research Archive
• Halvorsen, Charlotte Marie; Kolstad, Frode; Hald, John K; Johannesen, Tom Børge; Krossnes, Bård Kronen & Langmoen, Iver Arne [Show all 11 contributors for this article] (2010). Long-term Outcome After Resection of Intraspinal Ependymomas: Report of 86 Consecutive Cases. Neurosurgery. ISSN 0148-396X. 67(6), p. 1622–1631. doi: 10.1227/NEU.0b013e3181f96d41. Full text in Research Archive
• Spetalen, Signe; Sandvik, Leiv; Blomhoff, Svein & Jacobsen, Morten (2009). Rectal Visceral Sensitivity in Women with Irritable Bowel Syndrome without Psychiatric Comorbidity Compared with Healthy Volunteers. Gastroenterology Research and Practice. ISSN 1687-6121. 2009. doi: 10.1155/2009/130684. Full text in Research Archive

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• Tjønnfjord, Geir Erland; Loraas, Arne; Spetalen, Signe; Osnes, Liv Toril Nygård & Tveten, Kristian (2026). Congenital Dyserythropoietic Anemia Type II Caused by a New <i>SEC23B</i> Sequence Variant. doi: 10.1155/crh/7158943. Full text in Research Archive Show summary

  Congenital dyserythropoietic anemias (CDAs) include a heterogeneous group of conditions characterized by insufficient erythropoiesis giving rise to monolinear cytopenia. Based on the morphological features of erythroblasts, three major subtypes have been established: CDA Type I, CDA Type II, and CDA Type III. CDA Type II is the most common type of CDAs, and this disease is characterized by a normocytic anemia with a normal or slightly increased reticulocyte count. The bone marrow is hypercellular with erythroid hyperplasia and binucleated erythroblasts with two nuclei at the same maturation stage. The inheritance is autosomal recessive, and the disease is caused by biallelic mutations in the SEC28B gene. More than 100 pathogenetic variants have been identified. Here, we report on three patients from Somalia with CDA Type II caused by a new SEC23B sequence variant. They came to attention and were diagnosed in early adulthood. Cases 1 and 2 had mild anemia with signs of hemolysis, and Case 3 had mild anemia with reticulocytosis. The eosin‐5‐maleimide binding test showed reduced binding in all three patients. Molecular genetics disclosed homozygosity for the sequence variant NM_006363.6:c.1580T > C p.(Leu527Ser) in the SEC23B gene. A bone marrow aspirate was performed from Case 2, and the smear disclosed morphological abnormalities typical for CDA Type II.

• Tjønnfjord, Eirik; Tveten, Kristian; Spetalen, Signe & Tjønnfjord, Geir Erland (2025). ANKRD26 Gene Mutation and Thrombocytopenia—Is the Risk of Malignancy Dependent on the Mutation Variant? doi: 10.3390/hematolrep17040037. Full text in Research Archive Show summary

  Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid malignancies. However, the extent of this oncogenic risk appears to vary between specific gene variants. Understanding the genotype–phenotype relationship is essential for patient counseling and management. This report presents a multigenerational family carrying the rare c.−118C > G variant in the 5′ untranslated region of ANKRD26, contributing to the discussion on variant-specific cancer predisposition. Case Presentation: Two sisters aged 57 and 60 presented with lifelong bleeding diathesis and moderate thrombocytopenia. Their symptoms included easy bruising, menorrhagia, and excessive postoperative bleeding. Genetic testing confirmed heterozygosity for the ANKRD26 c.−118C > G variant. Bone marrow analysis revealed abnormal megakaryopoiesis without evidence of dysplasia or somatic mutations. One sister underwent major surgery without complications when managed with prophylactic hemostatic therapy. Their family history included multiple female relatives with similar symptoms, although formal testing was limited. Notably, none of the affected individuals developed hematologic malignancy, and only one developed esophageal cancer, with no current evidence linking this variant to solid tumors. Conclusions: This case underscores the importance of distinguishing between ANKRD26 variants when assessing malignancy risk. While ANKRD26-RT is associated with myeloid neoplasms, the c.−118C > G variant may confer a lower oncogenic potential. Variant-specific risk stratification and genetic counseling are crucial for optimizing surveillance and avoiding unnecessary interventions in low-risk individuals.

• Andersen, Kristin; Tjønnfjord, Geir Erland; Hestdalen, Malu Lian; Spetalen, Signe & Panagopoulos, Ioannis (2025). Complex Genetic Evolution and Treatment Challenges in Myeloid Neoplasms: A Case of Persistent t(2;3)(p15~23;q26)/ MECOM Rearrangement, SF3B1 Mutation, and Transient TNIP1::PDGFRB Chimera. doi: 10.21873/cgp.20483. Full text in Research Archive Show summary

  Background/Aim: Myelodysplastic syndromes (MDSs) are clonal bone marrow disorders characterized by ineffective hematopoiesis. They are classified based on morphology and genetic alterations, with SF3B1 variants linked to favorable prognosis and MECOM rearrangements associated with poor outcomes. The combined effects of these alterations remain unclear. We report an MDS patient carrying both SF3B1 and MECOM alterations who developed transient eosinophilia accompanied by a TNIP1::PDGFRB chimera in a subset of MECOM-affected cells. Case Report: A 73-year-old woman was diagnosed with myeloid neoplasia with excess blasts and multilineage dysplasia (MDS-EB1). Six months later, SF3B1 mutations were identified, leading to a diagnosis of MDS-SF3B1. Despite azacitidine treatment, her condition worsened, showing hypercellular bone marrow and eosinophilia. Genetic analysis revealed a t(2;3)(p15~23;q26)/MECOM rearrangement and TNIP1::PDGFRB chimera. Imatinib eradicated eosinophilia and reduced TNIP1::PDGFRB-positive cells, but the MECOM-clone persisted. Subsequent treatments, including hydroxyurea, mercaptopurine, and low-dose cytarabine, were ineffective. FLT3 mutations and high EVI1 transcript levels were later detected. The patient succumbed to progressive disease. Conclusion: This case highlights the complexity of MDS and the importance of genetic abnormalities in treatment planning. Persistent MECOM rearrangement and the TNIP1::PDGFRB chimera emphasize the need for further research into resistance mechanisms.

• Zub, Kamila; Spetalen, Signe; Endre, Kim Magnus Advocaat; Hegna, Tone Olaug Aarholt; Tjønnfjord, Geir Erland & Lehne, Gustav [Show all 7 contributors for this article] (2024). A rapidly growing breast tumour in a young woman. JEADV Clinical Practice. 00(0), p. 1–4. doi: 10.1002/jvc2.584. Full text in Research Archive
• Lindahl, Jørn Petter Hanto; Barlinn, Regine; Abrahamsen, Ingerid Weum; Spetalen, Signe; Midtvedt, Karsten & Jenssen, Trond Geir (2022). Case Report: Pure Red Cell Aplasia Caused by Refractory Parvovirus B19 Infection After Pancreas Transplantation Alone. Frontiers in Medicine. 9. doi: 10.3389/fmed.2022.849783. Full text in Research Archive Show summary

  A multidisciplinary team of doctors is in charge or is involved in the follow-up of patients who undergo solid organ transplantation (SOT). Immunosuppressive drugs are required after SOT, some potential unwanted side effects can be difficult to detect, and physicians must be aware of potential pitfalls. We report a case of a recipient with brittle type 1 diabetes who experienced severe and refractory anemia after pancreas transplantation alone (PTA). Despite a broad diagnostic approach for anemia, the diagnosis was delayed. The patient had normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors in the bone marrow, compatible with pure red cell aplasia (PRCA). Analyses of serological parvovirus B19 anti-IgM and anti-IgG antibodies, including PCR, were initially inconclusive/negative. The diagnosis of parvovirus B19 infection was confirmed after bone marrow biopsy with immunohistochemical staining for parvovirus B19. A retrospective analysis revealed an early post-transplant primary parvovirus B19 infection. The patient was successfully treated with intravenous immunoglobulin (IVIg) therapy. There is a risk of diagnostic delay for the less common types of anemia following SOT. Parvovirus B19 infection-associated PRCA is curable in SOT recipients and should be actively considered in patients with persistent anemia and low reticulocytes.

• Malecka, Agnieszka Maria; Tierens, Anne; Østlie, Ingunn; Schmitz, Roland; Trøen, Gunhild & Spetalen, Signe [Show all 10 contributors for this article] (2015). Primary diffuse large B-cell lymphoma associated with clonally-related monoclonal B lymphocytosis indicates a common precursor cell. Haematologica. ISSN 0390-6078. 100(10), p. e415–e418. doi: 10.3324/haematol.2015.126656. Full text in Research Archive
• Midtvedt, Øyvind; Gran, Jan Tore; Solheim, Hanne; Kirkhus, Eva & Spetalen, Signe (2014). Ø. Midtvedt og medarbeidere svarer:. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 134(19), p. 1823–1823. doi: 10.4045/tidsskr.14.1151. Full text in Research Archive
• Kleiveland, Charlotte Ramstad; Hult, Lene Therese Olsen; Spetalen, Signe; Kaldhusdal, Magne; Christoffersen, Trine Eker & Bengtsson, Oskar [Show all 9 contributors for this article] (2012). protective role of a non-commensal methanotroph bacterium in a mouse model of colitis. Full text in Research Archive
• Hult, Lene Therese Olsen; Kleiveland, Charlotte Ramstad; Spetalen, Signe; Jacobsen, Morten & Lea, Tor Erling (2012). På sporet av et nytt behandlingsprinsipp for IBD. Full text in Research Archive

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