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Publications (10 of 20) Show all publications
Bergemalm, D., Ramström, S., Kardeby, C., Hultenby, K., Göthlin Eremo, A., Sihlbom, C., . . . Åström, M. (2021). Platelet proteome and function in X-linked thrombocytopenia with thalassemia and in silico comparisons with gray platelet syndrome. Haematologica, 106(11), 2947-2959
Open this publication in new window or tab >>Platelet proteome and function in X-linked thrombocytopenia with thalassemia and in silico comparisons with gray platelet syndrome
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2021 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 106, no 11, p. 2947-2959Article in journal (Refereed) Published
Abstract [en]

In X-linked thrombocytopenia with thalassemia (XLTT; OMIM 314050), caused by the mutation p.R216Q in exon 4 of the GATA1 gene, male hemizygous patients display macrothrombocytopenia, bleeding diathesis and a β-thalassemia trait. Herein, we describe findings in two unrelated Swedish XLTT families with a bleeding tendency exceeding what is expected from the thrombocytopenia. Blood tests revealed low P-PAI-1 and P-factor 5, and elevated S-thrombopoietin levels. Transmission electron microscopy showed diminished numbers of platelet α- and dense granules. The proteomes of isolated blood platelets from 5 male XLTT patients, compared to 5 gender- and age matched controls, were explored. Quantitative mass spectrometry showed alterations of 83 proteins (fold change ≥±1.2, q< .05). Of 46 downregulated proteins, 39 were previously reported to be associated with platelet granules. Reduced protein levels of PTGS1 and SLC35D3 were validated in megakaryocytes of XLTT bone marrow biopsies by immunohistochemistry. Platelet function testing by flow cytometry revealed low dense- and α-granule release and fibrinogen binding in response to ligation of receptors for ADP, the thrombin receptor PAR4 and the collagen receptor GPVI. Significant reductions of a number of α-granule proteins overlapped with a previous platelet proteomics investigation in the inherited macrothrombocytopenia gray platelet syndrome (GPS). In contrast, Ca2+ transporter proteins that facilitate dense granule release were downregulated in XLTT but upregulated in GPS. Ingenuity Pathway Analysis showed altered Coagulation System and Protein Ubiquitination pathways in the XLTT platelets. Collectively, the results revealed protein and functional alterations affecting platelet α- and dense granules in XLTT, probably contributing to bleeding.

Place, publisher, year, edition, pages
Ferrata Storti Foundation, 2021
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-86784 (URN)10.3324/haematol.2020.249805 (DOI)000715742000018 ()33054111 (PubMedID)2-s2.0-85093539442 (Scopus ID)
Funder
Region Örebro County, OLL-158661; OLL-164431; OLL-239301; OLL-255251; OLL-268261
Available from: 2020-10-26 Created: 2020-10-26 Last updated: 2021-11-30Bibliographically approved
Kozlowski, P., Kameran Behnam, K., Uggla, B. & Åström, M. (2020). Carfilzomib-induced hemolysis is noticeably common but rarely shows features of thrombotic microangiopathy: A retrospective study. European Journal of Haematology, 104(6), 588-593
Open this publication in new window or tab >>Carfilzomib-induced hemolysis is noticeably common but rarely shows features of thrombotic microangiopathy: A retrospective study
2020 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 6, p. 588-593Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Hemolysis is a sporadically reported but potentially serious side effect of the proteasome inhibitor carfilzomib. We aimed to investigate the frequency of hemolysis in an unselected cohort.

METHODS: We performed a retrospective, single-center study of the incidence of hemolysis in patients treated with carfilzomib, based mainly on consecutive haptoglobin levels. The patients were diagnosed with myeloma (n = 20), AL amyloidosis (n = 3), and light-chain deposition disease (n = 1). Carfilzomib treatment was applied after a median of 3 (range: 1-7) therapy lines.

RESULTS: Haptoglobin levels were normal/increased before, generally suppressed during, and normalized after treatment with carfilzomib. Very low haptoglobin (<0.1 g/L) implying the presence of hemolysis was observed in 16 of 24 (67%) patients during carfilzomib therapy. Hemolysis was mild in 11 of 16 (69%) affected patients, whereas 5 of 16 (31%) required transfusion. Severe hemolysis was explained by thrombotic microangiopathy (TMA) in one patient who died of the complication. Mechanisms were unclear in the remaining 15 patients.

CONCLUSIONS: Hemolysis was surprisingly common but mostly mild during carfilzomib treatment. However, the possibility of TMA should be kept in mind in this setting. Hypothetically, non-TMA hemolysis could be attributed to the accumulation of globin chains due to the suppression of eukaryotic translation initiation inhibition by carfilzomib.

Place, publisher, year, edition, pages
Munksgaard Forlag, 2020
Keywords
Hemolysis, neoplasia-myeloma and other plasma cell dyscrasias, proteasome inhibitors, thrombotic microangiopathies
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-80911 (URN)10.1111/ejh.13401 (DOI)000529825700009 ()32115785 (PubMedID)2-s2.0-85081718148 (Scopus ID)
Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2020-12-01Bibliographically approved
Åström, M., Welander, E., Pourlotfi, A., Abawi, A., Ahlstrand, E. & Ivarsson, M. (2018). Activated interferon signaling in cultured BMSC from myelofibrosis patients: core finding of a proteomic study. In: : . Paper presented at 2nd International Conference on Tissue Repair, Regeneration, and Fibrosis, Chania, Crete, Greece, June 13-16, 2018.
Open this publication in new window or tab >>Activated interferon signaling in cultured BMSC from myelofibrosis patients: core finding of a proteomic study
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-67255 (URN)
Conference
2nd International Conference on Tissue Repair, Regeneration, and Fibrosis, Chania, Crete, Greece, June 13-16, 2018
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2021-05-25Bibliographically approved
Åström, M., Tajeddinn, W., Karlsson, M. G., Linder, O., Palmblad, J. & Lindblad, P. (2018). Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma. Biomarker Insights, 13, Article ID UNSP 1177271918792246.
Open this publication in new window or tab >>Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma
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2018 (English)In: Biomarker Insights, E-ISSN 1177-2719, Vol. 13, article id UNSP 1177271918792246Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.

CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-gamma) and IL-1 alpha, for the 3 renal cell carcinoma cases compared with healthy blood donors.

CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
chemokine, IL-6, IL-10, monocytosis, paraneoplastic leukocytosis, autocrine signaling, multiplex, inflammatory response, precision medicine, biomarker
National Category
Immunology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:oru:diva-68648 (URN)10.1177/1177271918792246 (DOI)000441829800001 ()30147294 (PubMedID)2-s2.0-85060719764 (Scopus ID)
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2023-12-08Bibliographically approved
Welander, E., Åström, M., Enonge Fotabe, L., Kardeby, C., Tina, E., Elgbratt, K., . . . Ivarsson, M. (2018). Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis. In: : . Paper presented at Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018.
Open this publication in new window or tab >>Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-69350 (URN)
Conference
Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2022-02-09Bibliographically approved
Lennmyr, E. B., Kozlowski, P., Ahlberg, L., Bernell, P., Hulegårdh, E., Izarra, A. S., . . . Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL), G. A. (2018). Real-world data on first relapse of acute lymphoblastic leukemia in patients >55 years. Leukemia and Lymphoma, 59(10), 2470-2473
Open this publication in new window or tab >>Real-world data on first relapse of acute lymphoblastic leukemia in patients >55 years
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2018 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 10, p. 2470-2473Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxfordshire, United Kingdom: Taylor & Francis, 2018
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:oru:diva-64503 (URN)10.1080/10428194.2017.1416369 (DOI)000455166400026 ()29345172 (PubMedID)2-s2.0-85041015429 (Scopus ID)
Note

Funding Agencies:

Lions Cancer Foundation  

Selander Foundation  

Thureus Foundation, Uppsala, Sweden 

Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2023-12-08Bibliographically approved
Kozlowski, P., Lennmyr, E., Ahlberg, L., Bernell, P., Hulegårdh, E., Karbach, H., . . . The Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL), G. a. (2017). Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden. European Journal of Haematology, 99(2), 141-149
Open this publication in new window or tab >>Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden
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2017 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, no 2, p. 141-149Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials.

METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012.

RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T- ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status ≥2 influenced the choice of palliation. Intensive, palliative, and both approaches, resulted in complete remission rate 83/16/70%, and 3 year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count ≤35 × 10(9) /L, and age ≥75 years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year group.

CONCLUSIONS: We report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2017
Keywords
acute lymphoblastic leukemia, chemotherapy, elderly, epidemiology
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-57317 (URN)10.1111/ejh.12896 (DOI)000404936400005 ()28419558 (PubMedID)2-s2.0-85020727975 (Scopus ID)
Note

Funding Agencies:

Research Committee of Region Orebro County Council (Orebro/Sweden)  

Lions Cancer Foundation (Uppsala/Sweden) 

Available from: 2017-05-30 Created: 2017-05-30 Last updated: 2020-12-01Bibliographically approved
Bergfelt, E., Kozlowski, P., Ahlberg, L., Bernell, P., Hulegårdh, E., Karbach, H., . . . Hallböök, H. (2016). RELAPSE OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN OLDER/ELDERLY PATIENTS: A SWEDISH POPULATION-BASED STUDY. Paper presented at 21st Congress of the European-Hematology-Association, Copenhagen, Denmark, June 9-12, 2016. Haematologica, 101(Suppl. 1), 34-35
Open this publication in new window or tab >>RELAPSE OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN OLDER/ELDERLY PATIENTS: A SWEDISH POPULATION-BASED STUDY
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no Suppl. 1, p. 34-35Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Pavia, Italy: Ferrata Storti Foundation, 2016
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-51735 (URN)000379484600074 ()
Conference
21st Congress of the European-Hematology-Association, Copenhagen, Denmark, June 9-12, 2016
Available from: 2016-08-23 Created: 2016-08-23 Last updated: 2017-11-28Bibliographically approved
Åström, M. (2015). Clinical cases: Presentation, diagnosis, treatment and follow-up: Case 2 - Chuvash polycythemia. In: Sylvie Hermouet (Ed.), Congenital Erythrocytosis and Hereditary Thrombocytosis: Clinical presentation, diagnosis, treatment and follow-up. A practical guide with clinical cases.. Portugal: European cooperation in science and technology
Open this publication in new window or tab >>Clinical cases: Presentation, diagnosis, treatment and follow-up: Case 2 - Chuvash polycythemia
2015 (English)In: Congenital Erythrocytosis and Hereditary Thrombocytosis: Clinical presentation, diagnosis, treatment and follow-up. A practical guide with clinical cases. / [ed] Sylvie Hermouet, Portugal: European cooperation in science and technology , 2015Chapter in book (Other academic)
Place, publisher, year, edition, pages
Portugal: European cooperation in science and technology, 2015
National Category
Hematology
Research subject
Medical Genetics
Identifiers
urn:nbn:se:oru:diva-45928 (URN)978-989-20-5646-3 (ISBN)
Available from: 2015-09-25 Created: 2015-09-25 Last updated: 2018-07-01Bibliographically approved
Bergfelt, E., Kozlowski, P., Åström, M., Ahlberg, L., Bernell, P., Hulegårdh, E., . . . Hallböök, H. (2015). Prognosis in older/elderly patients with acute lymphoblastic leukaemia diagnosed 2005-2012: results from a Swedish population-based study. Paper presented at 20th Congress of European-Hematology-Association, Vienna, Austria, June 11-14, 2015. Haematologica, 100(Suppl. 1), 202-202
Open this publication in new window or tab >>Prognosis in older/elderly patients with acute lymphoblastic leukaemia diagnosed 2005-2012: results from a Swedish population-based study
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2015 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, no Suppl. 1, p. 202-202Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Pavia: Ferrata Storti Foundation, 2015
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-46175 (URN)000361204902037 ()
Conference
20th Congress of European-Hematology-Association, Vienna, Austria, June 11-14, 2015
Available from: 2015-10-19 Created: 2015-10-19 Last updated: 2018-07-02Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3384-4387

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