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Gene expression analysis identifies a genetic signature potentially associated with response to alpha-IFN in chronic phase CML patients
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. (Blodsjukdomar)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. (Cancer Pharmacology and Informatics)
Vise andre og tillknytning
2007 (engelsk)Inngår i: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 31, nr 7, s. 931-938Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2007. Vol. 31, nr 7, s. 931-938
Emneord [en]
Chronic myeloid leukemia, Gene expression profiling, Interferon, Microarray, Drug response, RNASE2, CEBP
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-95822DOI: 10.1016/j.leukres.2006.11.015ISI: 000247764300009PubMedID: 17207527OAI: oai:DiVA.org:uu-95822DiVA, id: diva2:170171
Tilgjengelig fra: 2007-04-25 Laget: 2007-04-25 Sist oppdatert: 2017-12-14bibliografisk kontrollert
Inngår i avhandling
1. Clinical and Experimental Studies in Chronic Myeloid Leukemia: Studies of Treatment Outcome, In Vitro Cellular Drug Resistance and Gene Expression
Åpne denne publikasjonen i ny fane eller vindu >>Clinical and Experimental Studies in Chronic Myeloid Leukemia: Studies of Treatment Outcome, In Vitro Cellular Drug Resistance and Gene Expression
2007 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2007. s. 77
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 256
Emneord
Medicine, chronic myeloid leukemia, adult, stem cell transplantation, mobilization of Ph-negative stem cells, in vitro assay, imatinib, gene expression, Medicin
Identifikatorer
urn:nbn:se:uu:diva-7841 (URN)978-91-554-6878-1 (ISBN)
Disputas
2007-05-16, Enghoffsalen, Akademiska Sjukhuset, Ingång 50, bv, Uppsala, 09:15
Opponent
Veileder
Tilgjengelig fra: 2007-04-25 Laget: 2007-04-25bibliografisk kontrollert

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