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Imatinib-mesylate enhances the maintenance of chronic myeloid leukemia stem cell potential in the absence of glucose
- Source :
- Stem Cell Research, Vol 28, Iss, Pp 33-38 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- The introduction of BCR/Abl tyrosine kinase inhibitors (TKI), such as imatinib-mesylate (IM), has revolutioned the treatment of chronic myeloid leukemia (CML). However, although extremely effective in inducing CML remission, IM is unable to eliminate leukemia stem cells (LSC). This is largely due to the suppression of BCR/Abl protein, driven by the reduction of energy supply due to oxygen or glucose shortage, in stem cell niches of bone marrow. Here, we investigated whether, in K562 and KCL22 CML cell cultures, glucose shortage induces refractoriness of stem cell potential to IM. In the absence of glucose, IM, while maintaining its detrimental effect on CML cell bulk, actually enhanced colony formation ability and stem cell potential. This was paralleled by an increased expression of the Nanog and Sox-2 stem cell markers. These evidences stress further the importance of developing strategies alternative to TKI capable to target LSC of CML. Keywords: Leukemia stem cell potential, Imatinib treatment, Chronic myeloid leukemia, BCR/Abl protein expression, BCR/Abl signaling, Glucose shortage
- Subjects :
- 0301 basic medicine
Homeobox protein NANOG
Cell Survival
TKi, Imatinib-mesylate, chronic myeloid leukemia, stem cell, metabolism
Fusion Proteins, bcr-abl
Biology
Stem cell marker
03 medical and health sciences
0302 clinical medicine
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
hemic and lymphatic diseases
Biomarkers, Tumor
medicine
Humans
neoplasms
lcsh:QH301-705.5
Tumor Stem Cell Assay
Cell Proliferation
ABL
SOXB1 Transcription Factors
Myeloid leukemia
Nanog Homeobox Protein
Cell Biology
General Medicine
medicine.disease
Leukemia
Glucose
030104 developmental biology
Imatinib mesylate
lcsh:Biology (General)
030220 oncology & carcinogenesis
Imatinib Mesylate
Neoplastic Stem Cells
Cancer research
Stem cell
K562 Cells
Developmental Biology
K562 cells
Subjects
Details
- Language :
- English
- ISSN :
- 18735061
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research
- Accession number :
- edsair.doi.dedup.....ed62ed646bb9bc7615243fdf16e2d90a