Overexpression of c-<i>myb</i> in Leukaemic and Non-Leukaemic Variants of Cutaneous T-Cell Lymphoma

Abstract

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.

Sézary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3

“…18 Interestingly, we have previously reported that c-myb is consistently overexpressed in PBMC from SS patients, but not PBMC from MF patients. 19 Upregulated c-myb may well contribute to upregulation of CDO1 in SS PBMC indicating hierarchical pathways in the molecular pathogenesis of SS.…”

Sézary Syndrome Coexisting with B-Cell Chronic Lymphocytic Leukemia: Case Report and Review of the Literature

“…Considering the overlapping clinical features of T-prolymphocytic leukemia (previously known as T-CLL) and SS [56, 57], it is conceivable that if TCL1 expression persisted later in T-cell differentiation pathway than normal, perhaps through an epigenetic or posttranslational mechanism [58], then SS might develop. Alternatively, a genetic defect such as c-myb activation may contribute to the emergence of SS from TCL1 expressing precursor cells [59]. …”

c-Myb Immunoreactivity, Protein and mRNA Levels Significantly Increase in the Aged Hippocampus Proper in Gerbils

“…Myb genes (a-myb, b-myb and c-myb) are a family of transcription factors whose expressions have been implicated in the control of the proliferation and differentiation of normal and transformed cells [7]. Among these, c-myb proto-oncogene is the best characterized member of the myb family of transcription factor genes.…”