Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Cerny-Reiterer, S; Rabenhorst, A; Stefanzl, G; Herndlhofer, S; Hoermann, G; Müllauer, L; Baumgartner, S; Beham-Schmid, C; Sperr, WR; Mannhalter, C; Sill, H; Linkesch, W; Arock, M; Hartmann, K; Valent, P.
Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia.
Oncotarget. 2015; 6(5):3071-3084 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Beham-Schmid Christine
Linkesch Werner
Sill Heinz
Altmetrics:

Dimensions Citations:

Plum Analytics:
Number of Figures: 5
| | | | |
Abstract:
Although mast cells (MC) play an important role in allergic reactions, their physiologic role remains unknown. In mice, several models of MC-deficiency have been developed. However, no comparable human model is available. We examined the in vitro- and in vivo effects of the KIT-targeting drug imatinib on growth and development of human MC. Imatinib was found to inhibit stem cell factor (SCF)-induced differentiation of MC in long-term suspension cultures (IC50: 0.01 µM). Correspondingly, long-term treatment of chronic myeloid leukemia (CML) patients with imatinib (400 mg/day) resulted in a marked decrease in MC. In patients with continuous complete molecular response during therapy, bone marrow MC decreased to less than 5% of pre-treatment values, and also serum tryptase concentrations decreased significantly (pre-treatment: 32.0 ± 11.1 ng/ml; post-therapy: 3.4 ± 1.8, p<0.01). Other myeloid lineages, known to develop independently of KIT, were not affected by imatinib-therapy. Imatinib also produced a substantial decrease in MC-development in mice. However, no clinical syndrome attributable to drug-induced MC-deficiency was recorded in our CML patients. Together, imatinib suppresses MC production in vitro and in vivo. However, drug-induced MC depletion is not accompanied by adverse clinical events, suggesting that MC are less relevant to homeostasis in healthy tissues than we assumed so far.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Aged -
Animals -
Antineoplastic Agents - adverse effects
Cell Line, Tumor -
Dose-Response Relationship, Drug -
Female -
Gene Expression Regulation, Enzymologic -
Gene Expression Regulation, Neoplastic -
Humans -
Imatinib Mesylate - adverse effects
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - enzymology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology
Male -
Mast Cells - drug effects
Mast Cells - enzymology
Mast Cells - immunology
Mice, Inbred BALB C -
Mice, Inbred C57BL -
Middle Aged -
Protein Kinase Inhibitors - adverse effects
Proto-Oncogene Proteins c-kit - antagonists & inhibitors
Proto-Oncogene Proteins c-kit - genetics
Proto-Oncogene Proteins c-kit - metabolism
Time Factors -
Treatment Outcome -
Tryptases - genetics
Tryptases - metabolism
Xenograft Model Antitumor Assays -

Find related publications in this database (Keywords)
Mast Cells
KIT
Imatinib
Mast Cell Deficiency
© Meduni Graz Impressum