uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Proximity extension assay-based plasma proteomics cannot predict relapse in chronic myeloid leukaemia patients stopping treatment with tyrosine kinase inhibitors (TKI) but reveal profound effects of long-term TKI treatment on plasma protein profiles
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Section of hematology, Uppsala University Hospital, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
Hematology research unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
Institut National de la Santé et de la Recherche Medicale (INSERM), CHU de Poitiers, Poitiers, France.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
National Category
Hematology
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-327172OAI: oai:DiVA.org:uu-327172DiVA, id: diva2:1129668
Available from: 2017-08-05 Created: 2017-08-05 Last updated: 2017-08-05
In thesis
1. Clinical and Immunological Studies in Chronic Myeloid Leukaemia
Open this publication in new window or tab >>Clinical and Immunological Studies in Chronic Myeloid Leukaemia
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chronic myeloid leukaemia (CML) is characterised by the constitutively active tyrosine kinase BCR-ABL. Standard treatment with tyrosine kinase inhibitors (TKI) in the chronic phase (CP) of CML conveys excellent long-term prognosis but is associated with side effects and costs. Treatment free remission (TFR) is possible in a proportion of patients discontinuing treatment after obtaining deep treatment responses but it is not fully known how to select the right patients for stopping attempts. Treatment of accelerated phase (AP) and blast crisis (BC) is more complicated and the prognosis more dismal. In this thesis, we have studied factors of importance for outcome in CML patients with focus on immunological factors and clinical management.

In a cohort of 32 newly diagnosed CP-CML patients, evidence of active immune escape mechanisms were found. These declined with the course of TKI treatment and at the same time, effector lymphocyte responses were elicited. These anti-leukaemia immune responses might help in the long-term control of CML. Multiple plasma protein markers were also measured with three multiplex platforms in a smaller cohort of patients (n=14). Inflammatory cytokines and other plasma proteins were affected by TKI treatment and multiplexing seems useful for finding potential biomarkers with biologic or prognostic significance in CML.

Patients progressing to AP/BC were studied in a population-based material from the Swedish CML register. Approximately 4% of TKI-treated CP-CML patients transformed to AP/BC within 2 years of diagnosis. Monitoring of treatment responses was suboptimal in 1/3 of these patients and the median survival was 1.4 years after diagnosis of AP/BC. Thus, minimising the risk of disease progression through strict adherence to guidelines for monitoring and treatment is essential.

In a cohort of patients (n=50) discontinuing TKI treatment within a large European trial, musculoskeletal pain was reported by 30% of patients, starting within 1- 6 weeks of TKI discontinuation and spontaneously resolving over time in most cases. Patients (n=56) were also evaluated with a multiplex platform with a total of 162 inflammation- and cancer-related plasma proteins. No predictive protein biomarkers for successful TKI discontinuation could be found. However, profound effects of TKI-treatment were seen and plasma proteomics could be useful for understanding effects of long-term TKI-treatment.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. p. 62
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1347
Keywords
chronic myeloid leukaemia, accelerated phase, blast crisis, tyrosine kinase inhibitor, immunology, myeloid-derived suppressor cells, cytokines, proteomics, TKI discontinuation, population-based
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-324272 (URN)978-91-513-0021-4 (ISBN)
Public defence
2017-09-22, Enghoffsalen, Akademiska sjukhuset, Ingång 50, bv, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2017-09-01 Created: 2017-08-05 Last updated: 2017-09-08

Open Access in DiVA

No full text in DiVA

By organisation
Department of Medical SciencesDepartment of StatisticsDepartment of Immunology, Genetics and Pathology
Hematology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 337 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf