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Rosenquist, Richard
Alternative names
Publications (10 of 233) Show all publications
Polychronidou, E., Kalamaras, I., Agathangelidis, A., Sutton, L. A., Yan, X.-J., Bikos, V., . . . Tzovaras, D. (2018). Automated shape-based clustering of 3D immunoglobulin protein structures in chronic lymphocytic leukemia. BMC Bioinformatics, 19, Article ID 414.
Open this publication in new window or tab >>Automated shape-based clustering of 3D immunoglobulin protein structures in chronic lymphocytic leukemia
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2018 (English)In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 19, article id 414Article in journal (Refereed) Published
Abstract [en]

Background: Although the etiology of chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, is still unclear, strong evidence implicates antigen involvement in disease ontogeny and evolution. Primary and 3D structure analysis has been utilised in order to discover indications of antigenic pressure. The latter has been mostly based on the 3D models of the clonotypic B cell receptor immunoglobulin (BcR IG) amino acid sequences. Therefore, their accuracy is directly dependent on the quality of the model construction algorithms and the specific methods used to compare the ensuing models. Thus far, reliable and robust methods that can group the IG 3D models based on their structural characteristics are missing. Results: Here we propose a novel method for clustering a set of proteins based on their 3D structure focusing on 3D structures of BcR IG from a large series of patients with CLL. The method combines techniques from the areas of bioinformatics, 3D object recognition and machine learning. The clustering procedure is based on the extraction of 3D descriptors, encoding various properties of the local and global geometrical structure of the proteins. The descriptors are extracted from aligned pairs of proteins. A combination of individual 3D descriptors is also used as an additional method. The comparison of the automatically generated clusters to manual annotation by experts shows an increased accuracy when using the 3D descriptors compared to plain bioinformatics-based comparison. The accuracy is increased even more when using the combination of 3D descriptors. Conclusions: The experimental results verify that the use of 3D descriptors commonly used for 3D object recognition can be effectively applied to distinguishing structural differences of proteins. The proposed approach can be applied to provide hints for the existence of structural groups in a large set of unannotated BcR IG protein files in both CLL and, by logical extension, other contexts where it is relevant to characterize BcR IG structural similarity. The method does not present any limitations in application and can be extended to other types of proteins.

Keywords
CLL protein clustering, 3D protein descriptors, descriptor fusion
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-373247 (URN)10.1186/s12859-018-2381-1 (DOI)000454362600006 ()30453883 (PubMedID)
Funder
EU, Horizon 2020, 692298
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Wasik, A. M., Wu, C., Mansouri, L., Rosenquist, R., Pan-Hammarstrom, Q. & Sander, B. (2018). Clinical and functional impact of recurrent S1PR1 mutations in mantle cell lymphoma. BLOOD ADVANCES, 2(6), 621-625
Open this publication in new window or tab >>Clinical and functional impact of recurrent S1PR1 mutations in mantle cell lymphoma
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2018 (English)In: BLOOD ADVANCES, ISSN 2473-9529, Vol. 2, no 6, p. 621-625Article in journal (Refereed) Published
Place, publisher, year, edition, pages
AMER SOC HEMATOLOGY, 2018
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-354348 (URN)10.1182/bloodadvances.2017014860 (DOI)000428386900004 ()29549086 (PubMedID)
Funder
Swedish Research CouncilEU, European Research Council, RNAEDIT-649019Knut and Alice Wallenberg Foundation
Available from: 2018-06-27 Created: 2018-06-27 Last updated: 2018-06-27Bibliographically approved
Mansouri, L., Wierzbinska, J. A., Plass, C. & Rosenquist, R. (2018). Epigenetic deregulation in chronic lymphocytic leukemia: Clinical and biological impact. Seminars in Cancer Biology, 51, 1-11
Open this publication in new window or tab >>Epigenetic deregulation in chronic lymphocytic leukemia: Clinical and biological impact
2018 (English)In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 51, p. 1-11Article in journal (Refereed) Published
Abstract [en]

Deregulated transcriptional control caused by aberrant DNA methylation and/or histone modifications is a hallmark of cancer cells. In chronic lymphocytic leukemia (CLL), the most common adult leukemia, the epigenetic 'landscape' has added a new layer of complexity to our understanding of this clinically and biologically heterogeneous disease. Early studies identified aberrant DNA methylation, often based on single gene promoter analysis with both biological and clinical impact. Subsequent genome-wide profiling studies revealed differential DNA methylation between CLLs and controls and in prognostics subgroups of the disease. From these studies, it became apparent that DNA methylation in regions outside of promoters, such as enhancers, is important for the regulation of coding genes as well as for the regulation of non-coding RNAs. Although DNA methylation profiles are reportedly stable over time and in relation to therapy, a higher epigenetic heterogeneity or 'burden' is seen in more aggressive CLL subgroups, albeit as non-recurrent 'passenger' events. More recently, DNA methylation profiles in CLL analyzed in relation to differentiating normal B-cell populations revealed that the majority of the CLL epigenome reflects the epigenomes present in the cell of origin and that only a small fraction of the epigenetic alterations represents truly CLL-specific changes. Furthermore, CLL patients can be grouped into at least three clinically relevant epigenetic subgroups, potentially originating from different cells at various stages of differentiation and associated with distinct outcomes. In this review, we summarize the current understanding of the DNA methylome in CLL, the role of histone modifying enzymes, highlight insights derived from animal models and attempts made to target epigenetic regulators in CLL along with the future directions of this rapidly advancing field.

Place, publisher, year, edition, pages
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2018
Keywords
Chronic lymphocytic leukemia, DNA methylation, Histone modification, Outcome, Prognosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-364003 (URN)10.1016/j.semcancer.2018.02.001 (DOI)000442066000002 ()29427646 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationSwedish Cancer SocietyThe Karolinska Institutet's Research Foundation
Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2018-11-05Bibliographically approved
Malcikova, J., Tausch, E., Rossi, D., Sutton, L. A., Soussi, T., Zenz, T., . . . Pospisilova, S. (2018). ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—update on methodological approaches and results interpretation. Leukemia, 32(5), 1070-1080
Open this publication in new window or tab >>ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—update on methodological approaches and results interpretation
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2018 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 5, p. 1070-1080Article, review/survey (Refereed) Published
Abstract [en]

In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i.e., inhibitors of B-cell receptor (BcR) signaling and anti-apoptotic BCL2 family members, owing to their efficacy in patients with TP53 defects. In this report, the TP53 Network of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) presents updated recommendations on the methodological approaches for TP53 mutation analysis. Moreover, it provides guidance to ensure that the analysis is performed in a timely manner for all patients requiring treatment and that the data is interpreted and reported in a consistent, standardized, and accurate way. Since next-generation sequencing technologies are gaining prominence within diagnostic laboratories, this report also offers advice and recommendations for the interpretation of TP53 mutation data generated by this methodology.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-358110 (URN)10.1038/s41375-017-0007-7 (DOI)000431769800003 ()29467486 (PubMedID)
Funder
EU, Horizon 2020, 692298; 644906; LQ1601German Research Foundation (DFG), SFB1074Swedish Cancer SocietySwedish Research Council, FNBr 65269705; FM MU ROZV/24/LF/2016
Available from: 2018-08-24 Created: 2018-08-24 Last updated: 2018-08-24Bibliographically approved
Agathangelidis, A., Ljungström, V., Scarfo, L., Fazi, C., Gounari, M., Pandzic, T., . . . Ghia, P. (2018). Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations. Haematologica, 103(5), 865-873
Open this publication in new window or tab >>Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations
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2018 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 5, p. 865-873Article in journal (Refereed) Published
Abstract [en]

Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we per-formed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistinguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations. Exonic mutations were not frequently identified in putative chronic lymphocytic leukemia driver genes in all settings, including low-count monoclonal B-cell lymphocytosis. To corroborate these findings, we also performed deep sequencing in 11 known frequently mutated genes in an extended cohort of 28 monoclonal B-cell lym phocytosis/chronic lymphocytic leukemia cases. Interestingly, shared mutations were detected between clonal B cells and paired polymorphonuclear cells, strengthening the notion that at least a fraction of somatic mutations may occur before disease onset, likely at the hematopoietic stem cell level. Finally, we identified previously unreported non-coding variants targeting pathways relevant to B-cell and chronic lymphocytic leukemia development, likely associated with the acquisition of the characteristic neoplastic phenotype typical of both monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.

National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-356089 (URN)10.3324/haematol.2017.177212 (DOI)000431396200029 ()29449433 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyEU, European Research Council
Available from: 2018-07-19 Created: 2018-07-19 Last updated: 2018-07-19Bibliographically approved
Baliakas, P., Mattsson, M., Hadzidimitriou, A., Minga, E., Agathangelidis, A., Sutton, L. A., . . . Stamatopoulos, K. (2018). No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy [Letter to the editor]. Haematologica, 103(4), E158-E161
Open this publication in new window or tab >>No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy
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2018 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 4, p. E158-E161Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2018
National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-356894 (URN)10.3324/haematol.2017.182634 (DOI)000428242100006 ()29269523 (PubMedID)
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09Bibliographically approved
Amarasinghe, H., Wojdacz, T., Rose-Zerilli, M., Beattie, A., Forster, J., Kadalayil, L., . . . Strefford, J. (2018). Patients with a Memory-like DNA Methylation Signature exhibit long-term survival after first-line immuno-chemotherapy: Data from the UK CLL4, ARCTIC and ADMIRE trials. Paper presented at 58th Annual Scientific Meeting of the British-Society-for-Haematology, APR 16-18, 2018, Liverpool, ENGLAND. British Journal of Haematology, 181, 29-29
Open this publication in new window or tab >>Patients with a Memory-like DNA Methylation Signature exhibit long-term survival after first-line immuno-chemotherapy: Data from the UK CLL4, ARCTIC and ADMIRE trials
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2018 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, p. 29-29Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2018
Keywords
Chemo-immunotherapy, Chronic Lymphocytic Leukaemia, Clinical Trials, DNA methylation
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-357326 (URN)000430117900026 ()
Conference
58th Annual Scientific Meeting of the British-Society-for-Haematology, APR 16-18, 2018, Liverpool, ENGLAND
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Rawstron, A. C., Kreuzer, K.-A., Soosapilla, A., Spacek, M., Stehlikova, O., Gambell, P., . . . Montserrat, E. (2018). Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project. Cytometry. Part B, Clinical cytometry., 94(1), 121-128
Open this publication in new window or tab >>Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project
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2018 (English)In: Cytometry. Part B, Clinical cytometry., ISSN 1552-4949, E-ISSN 1552-4957, Vol. 94, no 1, p. 121-128Article in journal (Refereed) Published
Abstract [en]

The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as “required” or “recommended” for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate “required” markers using normal peripheral blood was developed. Responses were received from 150 participants with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5–20 in 82/150 (55%), and <5 cases per week in 45/150 (30%). The consensus for “required” diagnostic markers included: CD19, CD5, CD20, CD23, Kappa, and Lambda. “Recommended” markers potentially useful for differential diagnosis were: CD43, CD79b, CD81, CD200, CD10, and ROR1. Reproducible criteria for component reagents were assessed retrospectively in 14,643 cases from 13 different centers and showed >97% concordance with current approaches. A pilot study to validate staining quality was completed in 11 centers. Markers considered as “required” for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20, CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and practice. Importantly, a reproducible approach to validate and apply these markers in individual laboratories has been identified. Finally, a consensus “recommended” panel of markers to refine diagnosis in borderline cases (CD43, CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively evaluated.

Keywords
chronic lymphocytic leukemia, flow cytometry, diagnosis
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-346369 (URN)10.1002/cyto.b.21595 (DOI)000423805500012 ()29024461 (PubMedID)
Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2018-03-16Bibliographically approved
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A. H., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

National Category
Cancer and Oncology Urology and Nephrology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-325565 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-26 Created: 2019-01-07 Last updated: 2019-01-08Bibliographically approved
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A. H., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
Show others...
2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

National Category
Cancer and Oncology Urology and Nephrology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-325565 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2019-01-08Bibliographically approved
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