Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia

Cerny-Reiterer, Sabine and Rabenhorst, Anja and Stefanzl, Gabriele and Herndlhofer, Susanne and Hoermann, Gregor and Müllauer, Leonhard and Baumgartner, Sigrid and Beham-Schmid, Christine and Sperr, Wolfgang R. and Mannhalter, Christine and Sill, Heinz and Linkesch, Werner and Arock, Michel and Hartmann, Karin and Valent, Peter. (2015) Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia. Oncotarget, 6 (5). pp. 3071-3084.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/70767/

Downloads: Statistics Overview


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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Allergy and Immunity (Hartmann)
UniBasel Contributors:Hartmann, Karin
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 May 2020 14:26
Deposited On:23 May 2020 14:26

Repository Staff Only: item control page