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Impact of malignant...
Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients
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- Mustjoki, S (author)
- University of Helsinki, Finland
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- Richter, Johan (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Barbany, G (author)
- Karolinska Institutet
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- Ehrencrona, Hans (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine
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- Fioretos, Thoas (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine
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- Gedde-Dahl, T (author)
- Oslo university hospital, Norway
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Gjertsen, BT (author)
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- Hovland, R (author)
- Haukeland university hospital, Norway
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- Hernesniemi, S (author)
- University of Helsinki, Finland
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- Josefsen, D (author)
- The noewegian radium hospital, Norway
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- Koskenvesa, P (author)
- University of Helsinki, Finland,Norwegian University of Science and Technology, Norway
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- Dybedal, I (author)
- Oslo university hospital, Norway
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- Markevärn, Berit (author)
- Umeå universitet,Medicinska fakulteten,Umeå university hospital, Sweden
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- Olofsson, Tobias (author)
- Lund University,Lunds universitet,Institutionen för laboratoriemedicin,Medicinska fakulteten,Department of Laboratory Medicine,Faculty of Medicine
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- Olsson-Strömberg, Ulla (author)
- Uppsala universitet,Hematologi
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- Rapakko, K. (author)
- Oulo university hospital, Sweden
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- Thunberg, Sarah, 1976- (author)
- Karolinska Institutet, Stockholm, Sweden
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- Stenke, L. (author)
- Karolinska Institutet
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- Simonsson, Bengt (author)
- Uppsala universitet,Hematologi
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Porkka, K. (author)
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- Hjorth-Hansen, H. (author)
- Norwegian University of Science and Technology, Norway
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(creator_code:org_t)
- 2013-01-18
- 2013
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 27:7, s. 1520-1526
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- CML
- leukemia stem cell
- tyrosine kinase inhibitor
- progenitor
- CML
- leukemia stem cell
- tyrosine kinase inhibitor
- progenitor
Publication and Content Type
- ref (subject category)
- art (subject category)
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Leukemia
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
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Mustjoki, S
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Richter, Johan
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Barbany, G
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Ehrencrona, Hans
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Fioretos, Thoas
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Gedde-Dahl, T
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show more...
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Gjertsen, BT
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Hovland, R
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Hernesniemi, S
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Josefsen, D
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Koskenvesa, P
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Dybedal, I
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Markevärn, Berit
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Olofsson, Tobias
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Olsson-Strömberg ...
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Rapakko, K.
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Thunberg, Sarah, ...
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Stenke, L.
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Simonsson, Bengt
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Porkka, K.
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Hjorth-Hansen, H ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Leukemia
- By the university
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Umeå University
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Royal Institute of Technology
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Karolinska Institutet
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Uppsala University
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Lund University