Universität zu Köln

Cerny-Reiterer, Sabine, Rabenhorst, Anja, Stefanzl, Gabriele ORCID: 0000-0002-6759-4662, Herndlhofer, Susanne, Hoermann, Gregor ORCID: 0000-0002-7374-4380, Muellauer, Leonhard, Baumgartner, Sigrid, Beham-Schmid, Christine, Sperr, Wolfgang R., Mannhalter, Christine ORCID: 0000-0001-7667-8078, Sill, Heinz ORCID: 0000-0003-0993-4371, Linkesch, Werner, Arock, Michel, Hartmann, Karin ORCID: 0000-0002-4595-8226 and Valent, Peter ORCID: 0000-0003-0456-5095 (2015). Long-term treatment with imatinib results in profound mast cell deficiency in Ph plus chronic myeloid leukemia. Oncotarget, 6 (5). S. 3071 - 3085. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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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 mu M). 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cerny-Reiterer, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Rabenhorst, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Stefanzl, Gabriele UNSPECIFIED orcid.org/0000-0002-6759-4662 UNSPECIFIED Herndlhofer, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoermann, Gregor UNSPECIFIED orcid.org/0000-0002-7374-4380 UNSPECIFIED Muellauer, Leonhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Baumgartner, Sigrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Beham-Schmid, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Sperr, Wolfgang R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mannhalter, Christine UNSPECIFIED orcid.org/0000-0001-7667-8078 UNSPECIFIED Sill, Heinz UNSPECIFIED orcid.org/0000-0003-0993-4371 UNSPECIFIED Linkesch, Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Arock, Michel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Karin UNSPECIFIED orcid.org/0000-0002-4595-8226 UNSPECIFIED Valent, Peter UNSPECIFIED orcid.org/0000-0003-0456-5095 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-412199
DOI:	10.18632/oncotarget.3074
Journal or Publication Title:	Oncotarget
Volume:	6
Number:	5
Page Range:	S. 3071 - 3085
Date:	2015
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BONE-MARROW-TRANSPLANTATION; BLOOD MONONUCLEAR-CELLS; SYSTEMIC MASTOCYTOSIS; CLINICAL HEMATOLOGY; PROGENITOR CELLS; TYROSINE KINASE; TRYPTASE LEVELS; HOST-DEFENSE; IGE RECEPTOR; STEEL FACTOR Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41219