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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients

Author

  • S. Mustjoki
  • Johan Richter
  • G. Barbany
  • Hans Ehrencrona
  • Thoas Fioretos
  • T. Gedde-Dahl
  • B. T. Gjertsen
  • R. Hovland
  • S. Hernesniemi
  • D. Josefsen
  • P. Koskenvesa
  • I. Dybedal
  • B. Markevarn
  • Tobias Olofsson
  • U. Olsson-Stromberg
  • K. Rapakko
  • S. Thunberg
  • L. Stenke
  • B. Simonsson
  • K. Porkka
  • H. Hjorth-Hansen
Show all

Summary, in English

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.

Department/s

  • Division of Molecular Medicine and Gene Therapy
  • Division of Clinical Genetics
  • Department of Laboratory Medicine
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2013

Language

English

Pages

1520-1526

Publication/Series

Leukemia

Volume

27

Issue

7

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Keywords

  • CML
  • leukemia stem cell
  • tyrosine kinase inhibitor
  • progenitor

Status

Published

ISBN/ISSN/Other

  • ISSN: 1476-5551