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      Dasatinib-Induced Hypopigmentation in Pediatric Patient with Chronic Myeloid Leukemia: A Case Report and Review of the Literature

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          Abstract

          Dasatinib is an oral second-generation multitarget tyrosine-kinase inhibitor (TKI) that is efficacious in treating imatinib-resistant chronic myeloid leukemia (CML) or intolerant cases. Noncutaneous adverse effects with dasatinib are well known in the literature, most commonly cytopenias and fluid retention, while pigmentary abnormalities have rarely been reported. We report the case of a 12-year-old male known case of CML, who presented to dermatology clinic approximately 2 years after initiating dasatinib treatment, with new-onset hypopigmentation of his upper limb, upper chest, and both knees of six months' duration.

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          Most cited references 16

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          Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

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            The SCF/KIT pathway plays a critical role in the control of normal human melanocyte homeostasis.

            During development, the interaction of stem cell factor (SCF) with its receptor, KIT, is critical for the survival of melanocytes. Limited in vivo human studies have suggested a possible activating role of SCF on adult human melanocytes. In order to study the impact of this pathway on normal melanocyte homeostasis, human skin xenografts were treated with serial injections of recombinant human SCF or a KIT-inhibitory antibody (K44.2). On histologic evaluation, SCF injection increased, whereas KIT inhibition decreased the number, size, and dendricity of melanocytes. Immunohistochemical expression of melanocyte differentiation antigens, including tyrosinase-related-protein-1 and gp100/pmel17, was markedly increased by treatment with SCF, and decreased by K44.2 treatment. The number of Ki67-positive melanocytes was increased in the SCF-treated tissue, suggesting a direct proliferative effect of SCF; conversely, treatment with K44.2 resulted in melanocyte loss, which did not appear reversible with prolonged treatment. These findings demonstrate that the SCF/KIT pathway remains critical in adult human skin, and that pharmacologic modulation of this single pathway can control cutaneous melanocyte homeostasis.
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              Adverse cutaneous reactions secondary to tyrosine kinase inhibitors including imatinib mesylate, nilotinib, and dasatinib.

              Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis of these first- and second-generation TKIs' cutaneous side effects, and approaches to their treatment. The wide range of adverse effects clarifies the difficulty in designing a truly antitumoral TKI. © 2011 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                Journal
                Case Rep Dermatol Med
                Case Rep Dermatol Med
                CRIDM
                Case Reports in Dermatological Medicine
                Hindawi
                2090-6463
                2090-6471
                2018
                9 July 2018
                : 2018
                Affiliations
                1King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, P.O. Box 9515, Jeddah 21423, Saudi Arabia
                2Department of Dermatology, King Khaled National Guard Hospital, National Guard Health Affairs, P.O. Box 9515, Jeddah 21423, Saudi Arabia
                Author notes

                Academic Editor: Jacek Cezary Szepietowski

                Article
                10.1155/2018/4062431
                6077655
                Copyright © 2018 Bader Alharbi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Case Report

                Dermatology

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