BACKGROUND: In recent years, increasing attention has been focused on the skin hypopigmentation that develops after the initiation of imatinib mesylate therapy in patients with chronic myeloid leukaemia (CML). AIM: To understand the underlying mechanism of this hypopigmentation effect, and to explore the possibility of using imatinib in the treatment of pigmentation disorders. METHODS: We examined the effects of imatinib on the proliferation, apoptosis, melanin content and melanogenic activity of human primary epidermal melanocytes. The responsible molecular events were also investigated in a mechanism study. RESULTS: We found that imatinib led to a dramatic decrease in total melanin content in cultured melanocytes, by affecting melanocyte number and/or melanogenesis in a dose-dependent manner. This inhibition of melanogenesis was due to suppressed expression of tyrosinase and microphthalmia-associated transcription factor (MiTF). Furthermore, stem cell factor (SCF)-stimulated c-Kit activation and melanocyte proliferation were completely abrogated by imatinib. CONCLUSIONS: Inactivation of c-Kit signalling by imatinib has inhibitory effects on melanocyte survival, proliferation and melanogenesis, which explains the clinical hypopigmentation seen in patients with CML. These results also support using imatinib as a clinical depigmentation agent when dosage being carefully determined.
BACKGROUND: In recent years, increasing attention has been focused on the skin hypopigmentation that develops after the initiation of imatinib mesylate therapy in patients with chronic myeloid leukaemia (CML). AIM: To understand the underlying mechanism of this hypopigmentation effect, and to explore the possibility of using imatinib in the treatment of pigmentation disorders. METHODS: We examined the effects of imatinib on the proliferation, apoptosis, melanin content and melanogenic activity of human primary epidermal melanocytes. The responsible molecular events were also investigated in a mechanism study. RESULTS: We found that imatinib led to a dramatic decrease in total melanin content in cultured melanocytes, by affecting melanocyte number and/or melanogenesis in a dose-dependent manner. This inhibition of melanogenesis was due to suppressed expression of tyrosinase and microphthalmia-associated transcription factor (MiTF). Furthermore, stem cell factor (SCF)-stimulated c-Kit activation and melanocyte proliferation were completely abrogated by imatinib. CONCLUSIONS: Inactivation of c-Kit signalling by imatinib has inhibitory effects on melanocyte survival, proliferation and melanogenesis, which explains the clinical hypopigmentation seen in patients with CML. These results also support using imatinib as a clinical depigmentation agent when dosage being carefully determined.