Imatinib Mesylate Causes Hypopigmentation in the Skin

Anne S. Tsao, Hagop Kantarjian, Jorge Cortes, Susan O'Brien, Moshe Talpaz

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR-ABL protein in CML, c-kit (KIT) and platelet-derived growth factor receptors. In clinical trials with imatinib mesylate, common side effects of nausea, emesis, diarrhea, periorbital edema, fluid retention, and myelosuppression have been documented. METHODS. In this case series, the authors describe unique clinical findings of skin hypopigmentation in six patients with CML who were treated with imatinib mesylate. RESULTS. Most patients developed onset of skin hypopigmentation within the first month of treatment and all of the patients experienced additional drug toxicity. Despite patient susceptibility to toxicity, the presence of hypopigmentation did not appear to predict leukemic cell response or clinical outcome. All six patients established a hematologic response but only two patients had a complete cytogenetic response. Imatinib mesylate induced hypopigmentation also appeared to be reversible and potentially dose related. CONCLUSION. Skin hypopigmentation is a benign side effect from imatinib mesylate treatment that appears to be reversible upon discontinuation or dose reduction. Several lines of evidence have previously reported that KIT and its ligand stem cell factor (SCF) have a regulatory role in melanocyte development and survival, suggesting a rational mechanism of action for imatinib mesylate in the pathogenesis of hypopigmentation. The signal transduction mechanism currently is believed to involve SCF ligand binding of KIT and downstream activation of MAP kinase (Erk-2). Microphthalmia (Mi), a basic helix-loop-helix leucine zipper (bHL-HZip) transcription factor, is phosphorylated by MAP kinase at a serine residue (S73): Once phosphorylated, Mi transactivates the tyrosine pigmentation gene promoter and affects pigment production.

Original languageEnglish (US)
Pages (from-to)2483-2487
Number of pages5
JournalCancer
Volume98
Issue number11
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Hypopigmentation
Skin
Microphthalmos
Stem Cell Factor
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Ligands
Platelet-Derived Growth Factor Receptors
Melanocytes
Mitogen-Activated Protein Kinase 1
Pigmentation
Drug-Related Side Effects and Adverse Reactions
Cytogenetics
Protein-Tyrosine Kinases
Serine
Nausea
Vomiting
Tyrosine
Imatinib Mesylate
Diarrhea
Signal Transduction

Keywords

  • Chronic myelogenous leukemia (CML)
  • Imatinib mesylate
  • Skin depigmentation, MAP kinase, microphthalmia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tsao, A. S., Kantarjian, H., Cortes, J., O'Brien, S., & Talpaz, M. (2003). Imatinib Mesylate Causes Hypopigmentation in the Skin. Cancer, 98(11), 2483-2487. https://doi.org/10.1002/cncr.11812

Imatinib Mesylate Causes Hypopigmentation in the Skin. / Tsao, Anne S.; Kantarjian, Hagop; Cortes, Jorge; O'Brien, Susan; Talpaz, Moshe.

In: Cancer, Vol. 98, No. 11, 01.12.2003, p. 2483-2487.

Research output: Contribution to journalArticle

Tsao, AS, Kantarjian, H, Cortes, J, O'Brien, S & Talpaz, M 2003, 'Imatinib Mesylate Causes Hypopigmentation in the Skin', Cancer, vol. 98, no. 11, pp. 2483-2487. https://doi.org/10.1002/cncr.11812
Tsao AS, Kantarjian H, Cortes J, O'Brien S, Talpaz M. Imatinib Mesylate Causes Hypopigmentation in the Skin. Cancer. 2003 Dec 1;98(11):2483-2487. https://doi.org/10.1002/cncr.11812
Tsao, Anne S. ; Kantarjian, Hagop ; Cortes, Jorge ; O'Brien, Susan ; Talpaz, Moshe. / Imatinib Mesylate Causes Hypopigmentation in the Skin. In: Cancer. 2003 ; Vol. 98, No. 11. pp. 2483-2487.
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