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| Oncotarget. 2015 Mar 5. pii: 3074. pmc: PMC4413638 |
| Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia. |
| Cerny-Reiterer S1, Rabenhorst A2, Stefanzl G3, Herndlhofer S4, Hoermann G5, Müllauer L6, Baumgartner S7, Beham-Schmid C8, Sperr WR9, Mannhalter C10, Sill H11, Linkesch W12, Arock M13, Hartmann K14, Valent P15 |
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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 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. |
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Publikations ID: 25605011 Quelle: öffnen |
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