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
Gene expression analysis identifies a genetic signature potentially associated with response to alpha-IFN in chronic phase CML patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Blodsjukdomar)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Cancer Pharmacology and Informatics)
Show others and affiliations
2007 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 31, no 7, 931-938 p.Article in journal (Refereed) Published
Abstract [en]

Microarray-based gene expression analysis was performed on diagnostic chronic phase CML patient samples prior to interferon treatment. Fifteen patient samples corresponding to six cytogenetic responders and nine non-responders were included. Genes differentially expressed between responder and non-responder patients were listed and a subsequent leave-one-out cross validation (LOOV) procedure showed that the top 20 genes allowed the highest prediction accuracy. The relevant genes were quantified by real-time PCR that supported the microarray results. We conclude that it might be possible to use gene expression analysis to predict future response to interferon in CML diagnostic samples.

Place, publisher, year, edition, pages
2007. Vol. 31, no 7, 931-938 p.
Keyword [en]
Chronic myeloid leukemia, Gene expression profiling, Interferon, Microarray, Drug response, RNASE2, CEBP
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95822DOI: 10.1016/j.leukres.2006.11.015ISI: 000247764300009PubMedID: 17207527OAI: oai:DiVA.org:uu-95822DiVA: diva2:170171
Available from: 2007-04-25 Created: 2007-04-25 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Clinical and Experimental Studies in Chronic Myeloid Leukemia: Studies of Treatment Outcome, In Vitro Cellular Drug Resistance and Gene Expression
Open this publication in new window or tab >>Clinical and Experimental Studies in Chronic Myeloid Leukemia: Studies of Treatment Outcome, In Vitro Cellular Drug Resistance and Gene Expression
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aims of the studies described in the thesis were to investigate different treatment strategies in chronic myeloid leukemia (CML) patients. Furthermore, activity of imatinib was investigated by in vitro cytotoxicity assay, and the gene expression pattern in interferon treated patients.

In a randomized prospective national study, we examined the influence of busulphan (n=89) versus hydroxyurea (n=90) treatment on time to blast crisis, and survival. There was no significant difference in survival between hydroxyurea and busulphan treated patients; median survival was 3.5 and 3.2 years, respectively. The 26 patients who underwent allogeneic stem cell transplantation had a significantly longer median survival (4.7 years) than those who were not transplanted.

We investigated the feasibility of mobilizing Philadelphia chromosome negative blood stem cells with intensive chemotherapy and lenograstim in CML patients. Twenty-three patients (62%) were successfully mobilized. Twenty-one of these patients underwent autologous stem cell transplantation later on, with a 5-year overall survival at 68%.

Fluorometric Microculture Cytotoxicity Assay was used to analyze 32 tumor cell samples from CML patients, (26 chronic phase and 6 blast crisis). Imatinib showed a higher in vitro activity and more positive drug interactions in cells from blast crisis than from chronic phase. Interferon, daunorubicin and arsenic trioxide had the greatest benefit from a combination with imatinib.

Microarray-based gene expression analyses were performed on diagnostic CML samples prior to interferon treatment. We identified six genes that were differentially expressed in responders and non-responders to interferon. It might prove possible to use gene expression analysis to predict future response to interferon.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 77 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 256
Keyword
Medicine, chronic myeloid leukemia, adult, stem cell transplantation, mobilization of Ph-negative stem cells, in vitro assay, imatinib, gene expression, Medicin
Identifiers
urn:nbn:se:uu:diva-7841 (URN)978-91-554-6878-1 (ISBN)
Public defence
2007-05-16, Enghoffsalen, Akademiska Sjukhuset, Ingång 50, bv, Uppsala, 09:15
Opponent
Supervisors
Available from: 2007-04-25 Created: 2007-04-25Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Hagberg, AnetteGöransson, HannaIsaksson, AndersSimonsson, Bengt

Search in DiVA

By author/editor
Hagberg, AnetteGöransson, HannaIsaksson, AndersSimonsson, Bengt
By organisation
Department of Genetics and PathologyDepartment of Medical SciencesDepartment of Oncology, Radiology and Clinical Immunology
In the same journal
Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 491 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