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Leukemic Stem Cell ...
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Thielen, NoortjeVU University Medical Center, The Netherlands
(författare)
Leukemic Stem Cell Quantification in Newly Diagnosed Patients With Chronic Myeloid Leukemia Predicts Response to Nilotinib Therapy
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-205244
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-205244URI
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https://doi.org/10.1158/1078-0432.CCR-15-2791DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:134083183URI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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QC 20170419
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Purpose: Leukemic stem cells (LSCs) may harbor important resistance to tyrosine kinase inhibitors in chronic myelogenous leukemia (CML). We identified Philadelphia chromosome (Ph)-positive CD34(+)CD38(-) bone marrow cells (here denoted LSCs) and addressed their response-predictive value in patients with CML (n = 48) subjected to nilotinib in the ENEST1st trial (NCT01061177). Experimental design: Two flow cytometry-based cell sorting methods were used with multiparameter-directed CD45-(MPFC) and BCR-ABL1 probe-linked (FISH) identification of Ph-positive cells, respectively. Results: We observed a positive correlation between the proportion of LSCs at diagnosis and established prognostic markers (blast count, spleen size, Sokal score, and hemoglobin). Conversely, a high LSC burden predicted for an inferior molecular response at 3 (MPFC and FISH), 6 (MPFC), 9 (FISH), and 15 months (FISH). During nilotinib therapy, the proportion of LSCs decreased rapidly. At 3 months, a median of only 0.3% LSCs remained among CD34(+)CD38(-) cells, and in 33% of the patients the LSC clone was not detectable anymore (FISH). The response kinetics was similar in LSC fractions as it was in the progenitor and unseparated bone marrow cell fractions. Conclusions: The proportion of LSCs at diagnosis, as analyzed by two independent methodologies, reflects the biology of the disease and appeared as a prognostic and response-predictive marker in patients with CML subjected to first-line nilotinib therapy. (C) 2016 AACR.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Richter, JohanSkåne university hospital, Sweden
(författare)
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Baldauf, MatthiasMedical University of Innsbruck, Austria
(författare)
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Barbany, GiselaKarolinska Institutet
(författare)
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Fioretos, ThoasLund university, Sweden
(författare)
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Giles, FrancisRobertH. Lurie Comprehensive Cancer Center of Northwestern University, USA
(författare)
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Gjertsen, Bjorn-ToreUniversity of Bergen, Norway
(författare)
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Hochhaus, AndreasUniversit€atsklinikum Jena, Germany
(författare)
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Schuurhuis, Gerrit JanVU University Medical Center, The Netherlands
(författare)
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Sopper, SieghartInnsbruck Medical University and Tyrolean Cancer Research Institute, Austria
(författare)
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Stenke, LeifKarolinska Institutet
(författare)
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Thunberg, Sarah,1976-Karolinska university hospital, Sweden(Swepub:kth)u1rw1xrj
(författare)
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Wolf, DominikUniversity Clinic Bonn, Germany
(författare)
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Ossenkoppele, GertVU University Medical Center, The Netherlands
(författare)
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Porkka, KimmoHelsinki University Hospital, Finland
(författare)
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Janssen, JeroenVU University Medical Center, The Netherlands
(författare)
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Mustjoki, SatuUniversity of Helsinki, Finland
(författare)
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VU University Medical Center, The NetherlandsSkåne university hospital, Sweden
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Clinical Cancer Research22:16, s. 4030-40381078-04321557-3265
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Till lärosätets databas
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Thielen, Noortje
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Richter, Johan
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Baldauf, Matthia ...
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Barbany, Gisela
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Fioretos, Thoas
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Giles, Francis
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visa fler...
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Gjertsen, Bjorn- ...
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Hochhaus, Andrea ...
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Schuurhuis, Gerr ...
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Sopper, Sieghart
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Stenke, Leif
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Thunberg, Sarah, ...
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Wolf, Dominik
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Ossenkoppele, Ge ...
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Porkka, Kimmo
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Janssen, Jeroen
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Mustjoki, Satu
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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Clinical Cancer ...
- Av lärosätet
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Kungliga Tekniska Högskolan
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Karolinska Institutet