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

Direct link
Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients
Show others and affiliations
2013 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, no 7, 1520-1526 p.Article in journal (Refereed) Published
Abstract [en]

Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38=) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P = 0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P = 0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients.

Place, publisher, year, edition, pages
2013. Vol. 27, no 7, 1520-1526 p.
Keyword [en]
CML, leukemia stem cell, tyrosine kinase inhibitor, progenitor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-206461DOI: 10.1038/leu.2013.19ISI: 000321614000010OAI: oai:DiVA.org:uu-206461DiVA: diva2:644650
Available from: 2013-09-01 Created: 2013-08-30 Last updated: 2013-09-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Simonsson, Bengt
By organisation
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 190 hits
ReferencesLink to record
Permanent link

Direct link