Overexpression of c-myb in Leukaemic and Non-Leukaemic Variants of Cutaneous T-Cell Lymphoma

Background: The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL). Objective: Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL. Methods: c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR. Results: Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 ± 0.5) versus MF (1.2 ± 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 ± 31,960.32 AU in SS vs. 1,226.35 ± 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 × 10 –2 ± 2.27 × 10 –2 in SS vs. 0.91 × 10 –2 ± 1.18 × 10 –2 in MF vs. 0.24 × 10 –2 ± 0.11 × 10 –2 in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 × 10 –2 and 10.78 × 10 –2 ± 7.24 × 10 –2 ). Conclusion: Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.